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{{Short description|Molecule that carries genetic information}}
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'''Deoxyribonucleic acid''' ('''DNA''') is a ] that contains the ] instructions for the ] and function of ]. All known ] life and ] contain DNA. The main role of DNA in the cell is the long term storage of information. It is often compared to a ], since it contains the instructions to construct other components of the cell, such as ]s and ] molecules. The DNA segments that carry genetic information are called '']s'', but other DNA sequences have structural purposes, or are involved in regulating the expression of genetic information.
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] (type ]). The ]s in the structure are colour-coded by ] and the detailed structures of two ]s are shown in the bottom right.]]]
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'''Deoxyribonucleic acid''' ({{IPAc-en|audio=en-us-Deoxyribonucleic acid.ogg|d|iː|ˈ|ɒ|k|s|ᵻ|ˌ|r|aɪ|b|oʊ|nj|uː|ˌ|k|l|iː|ᵻ|k|,_|-|ˌ|k|l|eɪ|-}};<ref>{{MerriamWebsterDictionary|deoxyribonucleic acid}}</ref> '''DNA''') is a ] composed of two ] chains that coil around each other to form a ]. The polymer carries ] instructions for the development, functioning, growth and ] of all known ]s and many ]es. DNA and ] (RNA) are ]s. Alongside ]s, ] and complex carbohydrates (]s), nucleic acids are one of the four major types of ]s that are essential for all known forms of ].
In ]s such as animals and plants, DNA is stored inside the ], while in ]s such as ], the DNA is in the cell's ]. Unlike ], DNA does not act directly on other molecules; rather, various enzymes act on DNA and copy its information into either more DNA, in ], or ] it into protein. In ]s, ] proteins such as ]s compact and organize DNA, as well as helping control its interactions with other proteins in the nucleus.


The two DNA strands are known as polynucleotides as they are composed of simpler ]ic units called ]s.<ref>{{Cite book |vauthors= Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P |title= Molecular Biology of the Cell |edition= 6th |publisher= Garland |year= 2014 |url= http://www.garlandscience.com/product/isbn/9780815344322 |page= Chapter 4: DNA, Chromosomes and Genomes |isbn= 978-0-8153-4432-2 |url-status=live |archive-url= https://web.archive.org/web/20140714210549/http://www.garlandscience.com/product/isbn/9780815344322 |archive-date= 14 July 2014 |df= dmy-all }}</ref><ref>{{cite web | vauthors = Purcell A |title=DNA |url=http://basicbiology.net/micro/genetics/dna|website=Basic Biology |url-status=live |archive-url=https://web.archive.org/web/20170105045651/http://basicbiology.net/micro/genetics/dna/ |archive-date=5 January 2017}}</ref> Each nucleotide is composed of one of four ] ]s (] , ] , ] or ] ), a ] called ], and a ]. The nucleotides are joined to one another in a chain by ]s (known as the ]) between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating ]. The nitrogenous bases of the two separate polynucleotide strands are bound together, according to ]ing rules (A with T and C with G), with ]s to make double-stranded DNA. The complementary nitrogenous bases are divided into two groups, the single-ringed ]s and the double-ringed ]s. In DNA, the pyrimidines are thymine and cytosine; the purines are adenine and guanine.
DNA is a long ] of simple units called ]s, which are held together by a backbone made of sugars and phosphate groups. This backbone carries four types of molecules called ] and it is the sequence of these four bases that encodes information. The major function of DNA is to encode the sequence of ]s in ]s, using the ]. To read the genetic code, cells make a copy of a stretch of DNA in the nucleic acid ]. These RNA copies can then be used to direct ], but they can also be used directly as parts of ]s or ]s.


Both strands of double-stranded DNA store the same ]. This information is ] when the two strands separate. A large part of DNA (more than 98% for humans) is ], meaning that these sections do not serve as patterns for ]. The two strands of DNA run in opposite directions to each other and are thus ]. Attached to each sugar is one of four types of nucleobases (or ''bases''). It is the ] of these four nucleobases along the backbone that encodes genetic information. ] strands are created using DNA strands as a template in a process called ], where DNA bases are exchanged for their corresponding bases except in the case of thymine (T), for which RNA substitutes ] (U).<ref>{{Cite web|url=https://www.genome.gov/genetics-glossary/Uracil|title=Uracil|website=Genome.gov|language=en|access-date=21 November 2019}}</ref> Under the ], these RNA strands specify the sequence of ]s within proteins in a process called ].
==Physical and chemical properties==
]


Within eukaryotic cells, DNA is organized into long structures called ]s. Before typical ], these chromosomes are duplicated in the process of DNA replication, providing a complete set of chromosomes for each daughter cell. ] (]s, ]s, ] and ]s) store most of their DNA inside the ] as ], and some in the ] as ] or in ]s as ].<ref>{{cite book | vauthors = Russell P | title= iGenetics |url= https://archive.org/details/igenetics0000russ_v6o1 |url-access= registration |publisher= Benjamin Cummings |location= New York |year= 2001 |isbn= 0-8053-4553-1}}</ref> In contrast, ]s (] and ]) store their DNA only in the ], in ]s. Within eukaryotic chromosomes, ] proteins, such as ]s, compact and organize DNA. These compacting structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed.
DNA is a long ] made from repeating units called ]s.<ref name=Alberts>{{cite book | last = Alberts| first = Bruce| coauthors = Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walters | title = Molecular Biology of the Cell; Fourth Edition | publisher = Garland Science| date = 2002 | location = New York and London | url = http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=mboc4.TOC&depth=2 | id = ISBN 0-8153-3218-1}}</ref><ref name=Butler>Butler, John M. (2001) ''Forensic DNA Typing'' "Elsevier". pp. 14-15. ISBN 978-0-12-147951-0.</ref> The DNA chain is 22 to 24 ] wide and one nucleotide unit is 3.3&nbsp;angstroms long.<ref>{{cite journal | author = Mandelkern M, Elias J, Eden D, Crothers D | title = The dimensions of DNA in solution | journal = J Mol Biol | volume = 152 | issue = 1 | pages = 153-61 | year = 1981 | id = PMID 7338906}}</ref> Although these repeating units are very small, DNA polymers can be enormous molecules containing millions of nucleotides. For instance, the largest human ] is 220 million base pairs long.<ref>{{cite journal | author = Gregory S, ''et. al.'' | title = The DNA sequence and biological annotation of human chromosome 1 | journal = Nature | volume = 441 | issue = 7091 | pages = 315-21 | year = 2006 | id = PMID 16710414}}</ref>


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In living organisms, DNA does not usually exist as a single molecule, but instead as a tightly-associated pair of molecules.<ref name=Watson>{{cite journal | author = Watson J, Crick F | title = Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid | url=http://profiles.nlm.nih.gov/SC/B/B/Y/W/_/scbbyw.pdf | journal = Nature | volume = 171 | issue = 4356 | pages = 737-8 | year = 1953 | id = PMID 13054692}}</ref><ref name=berg>Berg J., Tymoczko J. and Stryer L. (2002) ''Biochemistry.'' W. H. Freeman and Company ISBN 0-7167-4955-6</ref> These two long strands entwine like vines, in the shape of a ]. The nucleotide repeats contain both the backbone of the molecule, which holds the chain together, and a base, which interacts with the other DNA strand in the helix. In general, a base linked to a sugar is called a ] and a base linked to a sugar and one or more phosphate groups is called a ]. If multiple nucleotides are linked together, as in DNA, this polymer is referred to as a ].<ref name=IUPAC> IUPAC-IUB Commission on Biochemical Nomenclature (CBN) Accessed 03 Jan 2006</ref>


== Properties ==
The backbone of the DNA strand is made from alternating ] and ] residues.<ref name=Ghosh>{{cite journal | author = Ghosh A, Bansal M | title = A glossary of DNA structures from A to Z | journal = Acta Crystallogr D Biol Crystallogr | volume = 59 | issue = Pt 4 | pages = 620-6 | year = 2003 | id = PMID 12657780}}</ref> The sugar in DNA is the ] (five carbon) sugar 2-deoxyribose. The sugars are joined together by phosphate groups that form ]s between the third and fifth carbon atoms in the sugar rings. These asymmetric bonds mean a strand of DNA has a direction. In a double helix the direction of the nucleotides in one strand is opposite to their direction in the other strand. This arrangement of DNA strands is called antiparallel. The asymmetric ends of a strand of DNA bases are referred to as the ] (''five prime'') and ] (''three prime'') ends. One of the major differences between DNA and RNA is the sugar, with 2-deoxyribose being replaced by the alternative pentose sugar ] in RNA.<ref name=berg/>
]s shown as dotted lines. Each end of the double helix has an exposed ] phosphate on one strand and an exposed ] hydroxyl group (—OH) on the other.]]


DNA is a long ] made from repeating units called ]s.<ref>{{cite book | vauthors = Saenger W |title= Principles of Nucleic Acid Structure |publisher= Springer-Verlag |location= New York |year= 1984 |isbn= 0-387-90762-9}}</ref><ref name="Alberts">{{cite book | vauthors = Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Peter W | title = Molecular Biology of the Cell | edition = Fourth | publisher = Garland Science | year = 2002 | location = New York and London | isbn = 0-8153-3218-1 | oclc = 145080076 | url = https://www.ncbi.nlm.nih.gov/books/NBK21054/ | url-status=live | archive-url = https://web.archive.org/web/20161101022040/https://www.ncbi.nlm.nih.gov/books/NBK21054/ | archive-date = 1 November 2016 | df = dmy-all }}</ref> The structure of DNA is dynamic along its length, being capable of coiling into tight loops and other shapes.<ref>{{cite journal | vauthors = Irobalieva RN, Fogg JM, Catanese DJ, Catanese DJ, Sutthibutpong T, Chen M, Barker AK, Ludtke SJ, Harris SA, Schmid MF, Chiu W, Zechiedrich L | title = Structural diversity of supercoiled DNA | journal = Nature Communications | volume = 6 | pages = 8440 | date = October 2015 | pmid = 26455586 | pmc = 4608029 | doi = 10.1038/ncomms9440 | bibcode = 2015NatCo...6.8440I |issn=2041-1723 }}</ref> In all species it is composed of two helical chains, bound to each other by ]. Both chains are coiled around the same axis, and have the same ] of {{convert|34|Å|nm|lk=on}}. The pair of chains have a radius of {{cvt|10|Å|nm}}.<ref name="Watson-1953">{{cite journal | vauthors = Watson JD, Crick FH | title = Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid | journal = Nature | volume = 171 | issue = 4356 | pages = 737–38 | date = April 1953 | pmid = 13054692 | doi = 10.1038/171737a0 | url = http://www.nature.com/nature/dna50/watsoncrick.pdf | bibcode = 1953Natur.171..737W | s2cid = 4253007 | url-status=live | archive-url = https://web.archive.org/web/20070204110320/http://www.nature.com/nature/dna50/watsoncrick.pdf | archive-date = 4 February 2007 | df = dmy-all |issn=0028-0836 }}</ref> According to another study, when measured in a different solution, the DNA chain measured {{cvt|22|-|26|Å|nm}} wide, and one nucleotide unit measured {{cvt|3.3|Å|nm}} long.<ref>{{cite journal | vauthors = Mandelkern M, Elias JG, Eden D, Crothers DM | title = The dimensions of DNA in solution | journal = Journal of Molecular Biology | volume = 152 | issue = 1 | pages = 153–61 | date = October 1981 | pmid = 7338906 | doi = 10.1016/0022-2836(81)90099-1|issn=0022-2836 }}</ref> The buoyant density of most DNA is 1.7g/cm<sup>3</sup>.<ref>{{cite journal |last1=Arrighi |first1=Frances E. |last2=Mandel |first2=Manley |last3=Bergendahl |first3=Janet |last4=Hsu |first4=T. C. |title=Buoyant densities of DNA of mammals |journal=Biochemical Genetics |date=June 1970 |volume=4 |issue=3 |pages=367–376 |doi=10.1007/BF00485753|pmid=4991030 |s2cid=27950750 |issn=0006-2928 }}</ref>
The DNA double helix is held together by ]s between the bases attached to the two strands. The four bases found in DNA are ] (abbreviated A), ] (C), ] (G) and ] (T). These four bases are shown below and are attached to the sugar/phosphate to form the complete nucleotide, as shown for adenosine monophosphate.


DNA does not usually exist as a single strand, but instead as a pair of strands that are held tightly together.<ref name="Watson-1953" /><ref name=berg>{{cite book | vauthors = Berg J, Tymoczko J, Stryer L | date = 2002 | title = Biochemistry | publisher = W.H. Freeman and Company | isbn = 0-7167-4955-6 }}</ref> These two long strands coil around each other, in the shape of a ]. The nucleotide contains both a segment of the ] of the molecule (which holds the chain together) and a ] (which interacts with the other DNA strand in the helix). A nucleobase linked to a sugar is called a ], and a base linked to a sugar and to one or more phosphate groups is called a ]. A ] comprising multiple linked nucleotides (as in DNA) is called a ].<ref name="IUPAC">{{cite journal | author = IUPAC-IUB Commission on Biochemical Nomenclature (CBN) | title = Abbreviations and Symbols for Nucleic Acids, Polynucleotides and their Constituents. Recommendations 1970 | journal = The Biochemical Journal | volume = 120 | issue = 3 | pages = 449–54 | date = December 1970 | pmid = 5499957 | pmc = 1179624 | doi = 10.1042/bj1200449 | url = http://www.chem.qmul.ac.uk/iupac/misc/naabb.html | archive-url = https://web.archive.org/web/20070205191106/http://www.chem.qmul.ac.uk/iupac/misc/naabb.html | url-status=dead | archive-date = 5 February 2007 |issn=0306-3283 }}</ref>
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<div style="border: none; width:500px;"><div class="thumbcaption">Structures of the four bases found in DNA and the nucleotide adenosine monophosphate.</div></div></div>


The backbone of the DNA strand is made from alternating ] and ] groups.<ref name=Ghosh>{{cite journal | vauthors = Ghosh A, Bansal M | title = A glossary of DNA structures from A to Z | journal = Acta Crystallographica Section D | volume = 59 | issue = Pt 4 | pages = 620–26 | date = April 2003 | pmid = 12657780 | doi = 10.1107/S0907444903003251| bibcode = 2003AcCrD..59..620G |issn=0907-4449 }}</ref> The sugar in DNA is ], which is a ] (five-]) sugar. The sugars are joined by phosphate groups that form ]s between the third and fifth carbon ]s of adjacent sugar rings. These are known as the ] (three prime end), and ] (five prime end) carbons, the prime symbol being used to distinguish these carbon atoms from those of the base to which the deoxyribose forms a ].<ref name="berg" />
These bases are classified into two types, adenine and guanine are fused five- and six-membered ]s called ]s, while cytosine and thymine are six-membered rings called ]s.<ref name=IUPAC/> A fifth pyrimidine base, called ] (U), replaces thymine in ] and differs from thymine by lacking a ] on its ring. Uracil is normally only found in DNA as a breakdown product of cytosine, but a very rare exception to this rule is a ] called PBS1 that contains uracil in its DNA.<ref name="nature1963-takahashi">{{cite journal | author=Takahashi I, Marmur J. | title=Replacement of thymidylic acid by deoxyuridylic acid in the deoxyribonucleic acid of a transducing phage for Bacillus subtilis | journal=Nature | year=1963 | pages=794-5 | volume=197 | id=PMID 13980287}}</ref>


Therefore, any DNA strand normally has one end at which there is a phosphate group attached to the 5′ carbon of a ribose (the 5′ phosphoryl) and another end at which there is a free hydroxyl group attached to the 3′ carbon of a ribose (the 3′ hydroxyl). The orientation of the 3′ and 5′ carbons along the sugar-phosphate backbone confers ] (sometimes called polarity) to each DNA strand. In a ], the direction of the nucleotides in one strand is opposite to their direction in the other strand: the strands are ]. The asymmetric ends of DNA strands are said to have a directionality of five prime end (5′ ), and three prime end (3′), with the 5′ end having a terminal phosphate group and the 3′ end a terminal hydroxyl group. One major difference between DNA and ] is the sugar, with the 2-deoxyribose in DNA being replaced by the related pentose sugar ] in RNA.<ref name="berg" />
</ref>]]


]).]]
The double helix is a right-handed spiral. As the DNA strands wind around each other, they leave gaps between each set of phosphate backbones, revealing the sides of the bases inside (see animation). There are two of these grooves twisting around the surface of the double helix: one groove is 22&nbsp;angstroms wide and the other 12&nbsp;angstroms wide.<ref>{{cite journal | author = Wing R, Drew H, Takano T, Broka C, Tanaka S, Itakura K, Dickerson R | title = Crystal structure analysis of a complete turn of B-DNA | journal = Nature | volume = 287 | issue = 5784 | pages = 755-8 | year = 1980 | id = PMID 7432492}}</ref> The larger groove is called the major groove, while the smaller, narrower groove is called the minor groove. The narrowness of the minor groove means that the edges of the bases are more accessible in the major groove. As a result, proteins like ]s that can bind to specific sequences in double-stranded DNA usually read the sequence by making contacts to the sides of the bases exposed in the major groove.<ref>{{cite journal | author = Pabo C, Sauer R | title = Protein-DNA recognition | journal = Annu Rev Biochem | volume = 53 | issue = | pages = 293-321 | year = | id = PMID 6236744}}</ref>


The DNA double helix is stabilized primarily by two forces: ]s between nucleotides and ] interactions among ] nucleobases.<ref name="Yakovchuk2006">{{cite journal | vauthors = Yakovchuk P, Protozanova E, Frank-Kamenetskii MD | title = Base-stacking and base-pairing contributions into thermal stability of the DNA double helix | journal = Nucleic Acids Research | volume = 34 | issue = 2 | pages = 564–74 | year = 2006 | pmid = 16449200 | pmc = 1360284 | doi = 10.1093/nar/gkj454 |issn=0305-1048 }}</ref> The four bases found in DNA are ] ({{mono|A}}), ] ({{mono|C}}), ] ({{mono|G}}) and ] ({{mono|T}}). These four bases are attached to the sugar-phosphate to form the complete nucleotide, as shown for ]. Adenine pairs with thymine and guanine pairs with cytosine, forming {{mono|A-T}} and {{mono|G-C}} ]s.<ref>{{cite book | vauthors = Tropp BE | title = Molecular Biology | edition = 4th | year = 2012 | publisher = Jones and Barlett Learning | location = Sudbury, Mass. | isbn = 978-0-7637-8663-2 }}</ref><ref>{{cite web | url = https://www.mun.ca/biology/scarr/Watson-Crick_Model.html | title = Watson-Crick Structure of DNA | year = 1953 | vauthors = Carr S | publisher = Memorial University of Newfoundland | access-date=13 July 2016 | url-status=live | archive-url = https://web.archive.org/web/20160719095721/http://www.mun.ca/biology/scarr/Watson-Crick_Model.html | archive-date = 19 July 2016 | df = dmy-all }}</ref>
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=== Nucleobase classification ===
|]
The nucleobases are classified into two types: the ]s, {{mono|A}} and {{mono|G}}, which are fused five- and six-membered ]s, and the ]s, the six-membered rings {{mono|C}} and {{mono|T}}.<ref name=berg /> A fifth pyrimidine nucleobase, ] ({{mono|U}}), usually takes the place of thymine in RNA and differs from thymine by lacking a ] on its ring. In addition to RNA and DNA, many artificial ]s have been created to study the properties of nucleic acids, or for use in biotechnology.<ref>{{cite journal | vauthors = Verma S, Eckstein F | title = Modified oligonucleotides: synthesis and strategy for users | journal = Annual Review of Biochemistry | volume = 67 | pages = 99–134 | year = 1998 | pmid = 9759484 |issn=0066-4154 | doi = 10.1146/annurev.biochem.67.1.99 | doi-access = free }}</ref>

=== Non-canonical bases ===

Modified bases occur in DNA. The first of these recognized was ], which was found in the ] of '']'' in 1925.<ref name=Johnson1925>{{cite journal | vauthors = Johnson TB, Coghill RD | year = 1925 | title = Pyrimidines. CIII. The discovery of 5-methylcytosine in tuberculinic acid, the nucleic acid of the tubercle bacillus. | journal = Journal of the American Chemical Society | volume = 47 | pages = 2838–44 | doi=10.1021/ja01688a030|issn=0002-7863}}</ref> The reason for the presence of these noncanonical bases in bacterial viruses (]s) is to avoid the ]s present in bacteria. This enzyme system acts at least in part as a molecular immune system protecting bacteria from infection by viruses.<ref name="pmid27319741">{{cite journal |vauthors=Weigele P, Raleigh EA |title=Biosynthesis and Function of Modified Bases in Bacteria and Their Viruses |journal=Chemical Reviews |volume=116 |issue=20 |pages=12655–12687 |date=October 2016 |pmid=27319741 |doi=10.1021/acs.chemrev.6b00114 |doi-access=free |issn=0009-2665 }}</ref> Modifications of the bases cytosine and adenine, the more common and modified DNA bases, play vital roles in the ] control of gene expression in plants and animals.<ref name="pmid30619465">{{cite journal |vauthors=Kumar S, Chinnusamy V, Mohapatra T |title=Epigenetics of Modified DNA Bases: 5-Methylcytosine and Beyond |journal=Frontiers in Genetics |volume=9 |pages=640 |date=2018 |pmid=30619465 |pmc=6305559 |doi=10.3389/fgene.2018.00640 |issn=1664-8021 |doi-access=free }}</ref>

A number of noncanonical bases are known to occur in DNA.<ref name="pmid28941008">{{cite journal | vauthors = Carell T, Kurz MQ, Müller M, Rossa M, Spada F | title = Non-canonical Bases in the Genome: The Regulatory Information Layer in DNA | journal = Angewandte Chemie | volume = 57 | issue = 16 | pages = 4296–4312 | date = April 2018 | pmid = 28941008 | doi = 10.1002/anie.201708228 }}</ref> Most of these are modifications of the canonical bases plus uracil.

* Modified '''Adenine'''
** N6-carbamoyl-methyladenine
** N6-methyadenine
* Modified '''Guanine'''
** 7-Deazaguanine
** 7-Methylguanine
* Modified '''Cytosine'''
** N4-Methylcytosine
** 5-Carboxylcytosine
** 5-Formylcytosine
** 5-Glycosylhydroxymethylcytosine
** 5-Hydroxycytosine
** 5-Methylcytosine
* Modified '''Thymidine'''
** α-Glutamythymidine
** α-Putrescinylthymine
* '''Uracil''' and modifications
** ]
** Uracil
** 5-Dihydroxypentauracil
** 5-Hydroxymethyldeoxyuracil
* Others
** Deoxyarchaeosine
** 2,6-Diaminopurine (2-Aminoadenine)

=== Grooves ===
] dye 33258.]]

Twin helical strands form the DNA backbone. Another double helix may be found tracing the spaces, or grooves, between the strands. These voids are adjacent to the base pairs and may provide a ]. As the strands are not symmetrically located with respect to each other, the grooves are unequally sized. The major groove is {{convert|22|Å|nm}} wide, while the minor groove is {{cvt|12|Å|nm}} in width.<ref>{{cite journal | vauthors = Wing R, Drew H, Takano T, Broka C, Tanaka S, Itakura K, Dickerson RE | title = Crystal structure analysis of a complete turn of B-DNA | journal = Nature | volume = 287 | issue = 5784 | pages = 755–58 | date = October 1980 | pmid = 7432492 | doi = 10.1038/287755a0 | bibcode = 1980Natur.287..755W | s2cid = 4315465 }}</ref> Due to the larger width of the major groove, the edges of the bases are more accessible in the major groove than in the minor groove. As a result, proteins such as ]s that can bind to specific sequences in double-stranded DNA usually make contact with the sides of the bases exposed in the major groove.<ref name="Pabo1984">{{cite journal | vauthors = Pabo CO, Sauer RT | title = Protein-DNA recognition | journal = Annual Review of Biochemistry | volume = 53 | pages = 293–321 | year = 1984 | pmid = 6236744 | doi = 10.1146/annurev.bi.53.070184.001453 }}</ref> This situation varies in unusual conformations of DNA within the cell ''(see below)'', but the major and minor grooves are always named to reflect the differences in width that would be seen if the DNA was twisted back into the ordinary ].

=== Base pairing ===
{{further|Base pair}}
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<div style="border: none; width:230px;"><div class="thumbcaption">At top, a '''GC''' base pair with three ]s. At the bottom, '''AT''' base pair with two hydrogen bonds. Hydrogen bonds (shown as dashed lines).</div></div></div> <div style="border: none; width:282px;"><div class="thumbcaption">Top, a '''{{mono|GC}}''' base pair with three ]s. Bottom, an '''{{mono|AT}}''' base pair with two hydrogen bonds. Non-covalent hydrogen bonds between the pairs are shown as dashed lines.</div></div></div>


In a DNA double helix, each type of nucleobase on one strand bonds with just one type of nucleobase on the other strand. This is called ] ]ing. Purines form ]s to pyrimidines, with adenine bonding only to thymine in two hydrogen bonds, and cytosine bonding only to guanine in three hydrogen bonds. This arrangement of two nucleotides binding together across the double helix (from six-carbon ring to six-carbon ring) is called a Watson-Crick base pair. DNA with high ] is more stable than DNA with low {{mono|GC}}-content. A ] (hydrogen bonding the 6-carbon ring to the 5-carbon ring) is a rare variation of base-pairing.<ref name="pmid23818176">{{cite journal |vauthors=Nikolova EN, Zhou H, Gottardo FL, Alvey HS, Kimsey IJ, Al-Hashimi HM |title=A historical account of Hoogsteen base-pairs in duplex DNA |journal=Biopolymers |volume=99 |issue=12 |pages=955–68 |year=2013 |pmid=23818176 |pmc=3844552 |doi=10.1002/bip.22334 }}</ref> As hydrogen bonds are not ], they can be broken and rejoined relatively easily. The two strands of DNA in a double helix can thus be pulled apart like a zipper, either by a mechanical force or high ].<ref>{{cite journal | vauthors = Clausen-Schaumann H, Rief M, Tolksdorf C, Gaub HE | title = Mechanical stability of single DNA molecules | journal = Biophysical Journal | volume = 78 | issue = 4 | pages = 1997–2007 | date = April 2000 | pmid = 10733978 | pmc = 1300792 | doi = 10.1016/S0006-3495(00)76747-6 | bibcode = 2000BpJ....78.1997C }}</ref> As a result of this base pair complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. This reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in organisms.<ref name=Alberts />
===Base pairing===
{{further|]}}
Each type of base on one strand forms a bond with just one type of base on the other strand. This is called complementary ]ing. Here, purines form ]s to pyrimidines, with A bonding only to T, and C bonding only to G. This arrangement of two nucleotides joined together across the double helix is called a base pair. In a double helix, the two strands are also held together by ]s generated by the ] and ], but these forces are not affected by the sequence of the DNA.<ref>{{cite journal | author = Ponnuswamy P, Gromiha M | title = On the conformational stability of oligonucleotide duplexes and tRNA molecules | journal = J Theor Biol | volume = 169 | issue = 4 | pages = 419-32 | year = 1994 | id = PMID 7526075}}</ref> As hydrogen bonds are not ], they can be broken and rejoined relatively easily. The two strands of DNA in a double helix can therefore be pulled apart like a zipper, either by a mechanical force or high temperature.<ref>{{cite journal | author = Clausen-Schaumann H, Rief M, Tolksdorf C, Gaub H | title = Mechanical stability of single DNA molecules | url=http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1300792&blobtype=pdf | journal = Biophys J | volume = 78 | issue = 4 | pages = 1997-2007 | year = 2000 | id = PMID 10733978}}</ref> As a result of this complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. Indeed, this reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in living organisms.<ref name=Alberts/>


{{Anchor|ssDNA}}
The two types of base pairs form different numbers of ]s, AT forming two hydrogen bonds, and GC forming three hydrogen bonds (see figures, left). The GC base-pair is therefore stronger than the AT base pair. As a result, it is both the percentage of GC base pairs and the overall length of a DNA double helix that determine the strength of the association between the two strands of DNA. Long DNA helices with a high GC content have strongly interacting strands, while short helices with high AT content have weakly interacting strands.<ref>{{cite journal | author = Chalikian T, Völker J, Plum G, Breslauer K | title = A more unified picture for the thermodynamics of nucleic acid duplex melting: a characterization by calorimetric and volumetric techniques | url=http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=22151&blobtype=pdf | journal = Proc Natl Acad Sci U S A | volume = 96 | issue = 14 | pages = 7853-8 | year = 1999 | id = PMID 10393911}}</ref> Parts of the DNA double helix that need to separate easily, such as the TATAAT ] in bacterial ]s, tend to have sequences with a high AT content, making the strands easier to pull apart.<ref>{{cite journal | author = deHaseth P, Helmann J | title = Open complex formation by Escherichia coli RNA polymerase: the mechanism of polymerase-induced strand separation of double helical DNA | journal = Mol Microbiol | volume = 16 | issue = 5 | pages = 817-24 | year = 1995 | id = PMID 7476180}}</ref> In the laboratory, the strength of this interaction can be measured by finding the temperature required to break the hydrogen bonds, their ] (also called ''T<sub>m</sub>'' value). When all the base pairs in a DNA double helix melt, the strands separate and exist in solution as two entirely independent molecules. These single-stranded DNA molecules have no single shape, but some conformations are more stable than others.<ref>{{cite journal | author = Isaksson J, Acharya S, Barman J, Cheruku P, Chattopadhyaya J | title = Single-stranded adenine-rich DNA and RNA retain structural characteristics of their respective double-stranded conformations and show directional differences in stacking pattern | journal = Biochemistry | volume = 43 | issue = 51 | pages = 15996-6010 | year = 2004 | id = PMID 15609994}}</ref> The base pairing, or lack of it, can create various topologies at the ]. These can be exploited in ].


===Sense and antisense=== ==== ssDNA vs. dsDNA ====
Most DNA molecules are actually two polymer strands, bound together in a helical fashion by noncovalent bonds; this double-stranded (dsDNA) structure is maintained largely by the intrastrand base stacking interactions, which are strongest for {{mono|G,C}} stacks. The two strands can come apart—a process known as melting—to form two single-stranded DNA (ssDNA) molecules. Melting occurs at high temperatures, low salt and high ] (low pH also melts DNA, but since DNA is unstable due to acid depurination, low pH is rarely used).
{{further|]}}


The stability of the dsDNA form depends not only on the {{mono|GC}}-content (% {{mono|G,C}} basepairs) but also on sequence (since stacking is sequence specific) and also length (longer molecules are more stable). The stability can be measured in various ways; a common way is the ] (also called ''T<sub>m</sub>'' value), which is the temperature at which 50% of the double-strand molecules are converted to single-strand molecules; melting temperature is dependent on ionic strength and the concentration of DNA. As a result, it is both the percentage of {{mono|GC}} base pairs and the overall length of a DNA double helix that determines the strength of the association between the two strands of DNA. Long DNA helices with a high {{mono|GC}}-content have more strongly interacting strands, while short helices with high {{mono|AT}} content have more weakly interacting strands.<ref>{{cite journal | vauthors = Chalikian TV, Völker J, Plum GE, Breslauer KJ | title = A more unified picture for the thermodynamics of nucleic acid duplex melting: a characterization by calorimetric and volumetric techniques | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 14 | pages = 7853–58 | date = July 1999 | pmid = 10393911 | pmc = 22151 | doi = 10.1073/pnas.96.14.7853 | bibcode = 1999PNAS...96.7853C | doi-access = free }}</ref> In biology, parts of the DNA double helix that need to separate easily, such as the {{mono|TATAAT}} ] in some ], tend to have a high {{mono|AT}} content, making the strands easier to pull apart.<ref>{{cite journal | vauthors = deHaseth PL, Helmann JD | title = Open complex formation by Escherichia coli RNA polymerase: the mechanism of polymerase-induced strand separation of double helical DNA | journal = Molecular Microbiology | volume = 16 | issue = 5 | pages = 817–24 | date = June 1995 | pmid = 7476180 | doi = 10.1111/j.1365-2958.1995.tb02309.x | s2cid = 24479358 }}</ref>
DNA is copied into RNA by ] enzymes that only work in the 5' to 3' direction.<ref name=Joyce>{{cite journal | author = Joyce C, Steitz T | title = Polymerase structures and function: variations on a theme? | url=http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=177480&blobtype=pdf | journal = J Bacteriol | volume = 177 | issue = 22 | pages = 6321-9 | year = 1995 | id = PMID 7592405}}</ref> A DNA sequence is called "sense" if its sequence is copied by these enzymes and then translated into protein. The sequence on the opposite strand is complementary to the sense sequence and is therefore called the "antisense" sequence. Both sense and antisense sequences can exist on different parts of the same strand of DNA. In both prokaryotes and eukaryotes, antisense sequences are transcribed, but the functions of these RNAs are not entirely clear.<ref>{{cite journal | author = Hüttenhofer A, Schattner P, Polacek N | title = Non-coding RNAs: hope or hype? | journal = Trends Genet | volume = 21 | issue = 5 | pages = 289-97 | year = 2005 | id = PMID 15851066}}</ref> One proposal is that antisense RNAs are involved in regulating gene expression through RNA-RNA base pairing.<ref>{{cite journal | author = Munroe S | title = Diversity of antisense regulation in eukaryotes: multiple mechanisms, emerging patterns | journal = J Cell Biochem | volume = 93 | issue = 4 | pages = 664-71 | year = 2004 | id = PMID 15389973}}</ref>


In the laboratory, the strength of this interaction can be measured by finding the melting temperature ''T<sub>m</sub>'' necessary to break half of the hydrogen bonds. When all the base pairs in a DNA double helix melt, the strands separate and exist in solution as two entirely independent molecules. These single-stranded DNA molecules have no single common shape, but some conformations are more stable than others.<ref>{{cite journal | vauthors = Isaksson J, Acharya S, Barman J, Cheruku P, Chattopadhyaya J | title = Single-stranded adenine-rich DNA and RNA retain structural characteristics of their respective double-stranded conformations and show directional differences in stacking pattern | journal = Biochemistry | volume = 43 | issue = 51 | pages = 15996–6010 | date = December 2004 | pmid = 15609994 | doi = 10.1021/bi048221v | url = http://www.boc.uu.se/boc14www/thesis/johan2005/Paper%20V/Paper%20V.pdf | url-status=live | archive-url = https://web.archive.org/web/20070610205112/http://www.boc.uu.se/boc14www/thesis/johan2005/Paper%20V/Paper%20V.pdf | archive-date = 10 June 2007 | df = dmy-all }}</ref>
A few DNA sequences in ] and ], and more in ] and ], blur the distinction made above between sense and antisense strands by having overlapping genes.<ref>{{cite journal | author = Makalowska I, Lin C, Makalowski W | title = Overlapping genes in vertebrate genomes | journal = Comput Biol Chem | volume = 29 | issue = 1 | pages = 1-12 | year = 2005 | id = PMID 15680581}}</ref> In these cases, some DNA sequences do double duty, encoding one protein when read 5' to 3' along one strand, and a second protein when read in the opposite direction (still 5' to 3') along the other strand. In bacteria, this overlap may be involved in the regulation of gene transcription.<ref>{{cite journal | author = Johnson Z, Chisholm S | title = Properties of overlapping genes are conserved across microbial genomes | journal = Genome Res | volume = 14 | issue = 11 | pages = 2268-72 | year = 2004 | id = PMID 15520290}}</ref> While in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome.<ref>{{cite journal | author = Lamb R, Horvath C | title = Diversity of coding strategies in influenza viruses | journal = Trends Genet | volume = 7 | issue = 8 | pages = 261-6 | year = 1991 | id = PMID 1771674}}</ref> Another way of reducing genome size is seen in some viruses that contain linear or circular single-stranded DNA as their genetic material.<ref>{{cite journal | author = Davies J, Stanley J | title = Geminivirus genes and vectors | journal = Trends Genet | volume = 5 | issue = 3 | pages = 77-81 | year = 1989 | id = PMID 2660364}}</ref><ref>{{cite journal | author = Berns K | title = Parvovirus replication | journal = Microbiol Rev | volume = 54 | issue = 3 | pages = 316-29 | year = 1990 | id = PMID 2215424}}</ref>


===Supercoiling=== === Amount ===
] of a human. It shows 22 ]s, both the female (XX) and male (XY) versions of the ] (bottom right), as well as the ] (to scale at bottom left). The blue scale to the left of each chromosome pair (and the mitochondrial genome) shows its length in terms of millions of DNA ]s.{{further|Karyotype}}]]
{{Further|]}}
In humans, the total female ] ] per cell extends for 6.37 Gigabase pairs (Gbp), is 208.23&nbsp;cm long and weighs 6.51 picograms (pg).<ref name="pmid30813969">{{cite journal| vauthors=Piovesan A, Pelleri MC, Antonaros F, Strippoli P, Caracausi M, Vitale L| title=On the length, weight and GC content of the human genome. | journal=BMC Res Notes | year= 2019 | volume= 12 | issue= 1 | pages= 106 | pmid=30813969 | doi=10.1186/s13104-019-4137-z | pmc=6391780 | doi-access=free }}</ref> Male values are 6.27 Gbp, 205.00&nbsp;cm, 6.41 pg.<ref name="pmid30813969"/> Each DNA polymer can contain hundreds of millions of nucleotides, such as in ]. Chromosome 1 is the largest human ] with approximately 220 million ]s, and would be {{val|85|u=mm}} long if straightened.<ref name="Gregory_2006" />
DNA can be twisted like a rope in a process called ]. Normally, with DNA in its "relaxed" state a strand circles the axis of the double helix once every 10.4 base pairs, but if the DNA is twisted the strands become more tightly or more loosely wound.<ref>{{cite journal | author = Benham C, Mielke S | title = DNA mechanics | journal = Annu Rev Biomed Eng | volume = 7 | issue = | pages = 21-53 | year = | id = PMID 16004565}}</ref> If the DNA is twisted in the direction of the helix this is positive supercoiling and the bases are held more tightly together. If they are twisted in the opposite direction this is negative supercoiling and the bases come apart more easily. In nature, most DNA has slight negative supercoiling that is introduced by enzymes called ]s.<ref name=Champoux>{{cite journal | author = Champoux J | title = DNA topoisomerases: structure, function, and mechanism | journal = Annu Rev Biochem | volume = 70 | issue = | pages = 369-413 | year = | id = PMID 11395412}}</ref> These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as ] and ].<ref name=Wang>{{cite journal | author = Wang J | title = Cellular roles of DNA topoisomerases: a molecular perspective | journal = Nat Rev Mol Cell Biol | volume = 3 | issue = 6 | pages = 430-40 | year = 2002 | id = PMID 12042765}}</ref>


In ]s, in addition to ], there is also ] (mtDNA) which encodes certain proteins used by the mitochondria. The mtDNA is usually relatively small in comparison to the nuclear DNA. For example, the ] forms closed circular molecules, each of which contains 16,569<ref name="Anderson_1981">{{cite journal | vauthors = Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, Schreier PH, Smith AJ, Staden R, Young IG | display-authors = 6 | title = Sequence and organization of the human mitochondrial genome | journal = Nature | volume = 290 | issue = 5806 | pages = 457–465 | date = April 1981 | pmid = 7219534 | doi = 10.1038/290457a0 | s2cid = 4355527 | bibcode = 1981Natur.290..457A }}</ref><ref>{{Cite web |url=http://chemistry.umeche.maine.edu/CHY431/MitoDNA.html |title=Untitled |access-date=2012-06-13 |archive-url=https://web.archive.org/web/20110813123936/http://chemistry.umeche.maine.edu/CHY431/MitoDNA.html |archive-date=2011-08-13 |url-status=dead }}</ref> DNA base pairs,<ref name=Satoh1991>{{cite journal | vauthors = Satoh M, Kuroiwa T | title = Organization of multiple nucleoids and DNA molecules in mitochondria of a human cell | journal = Experimental Cell Research | volume = 196 | issue = 1 | pages = 137–140 | date = September 1991 | pmid = 1715276 | doi = 10.1016/0014-4827(91)90467-9 }}</ref> with each such molecule normally containing a full set of the mitochondrial genes. Each human mitochondrion contains, on average, approximately 5 such mtDNA molecules.<ref name=Satoh1991/> Each human ] contains approximately 100 mitochondria, giving a total number of mtDNA molecules per human cell of approximately 500.<ref name=Satoh1991/> However, the amount of mitochondria per cell also varies by cell type, and an ] can contain 100,000 mitochondria, corresponding to up to 1,500,000 copies of the mitochondrial genome (constituting up to 90% of the DNA of the cell).<ref name="pmid28721182">{{cite journal | vauthors = Zhang D, Keilty D, Zhang ZF, Chian RC | title = Mitochondria in oocyte aging: current understanding | journal = Facts, Views & Vision in ObGyn | volume = 9 | issue = 1 | pages = 29–38 | date = March 2017 | pmid = 28721182 | pmc = 5506767 }}</ref>
]


=== Sense and antisense ===
===Alternative double-helical structures===
{{further|Sense (molecular biology)}}
{{Further|]}}


A ] is called a "sense" sequence if it is the same as that of a ] copy that is translated into protein.<ref> {{Webarchive|url=https://web.archive.org/web/20080424015915/http://www.chem.qmul.ac.uk/iubmb/newsletter/misc/DNA.html |date=24 April 2008 }} JCBN/NC-IUB Newsletter 1989. Retrieved 7 May 2008</ref> The sequence on the opposite strand is called the "antisense" sequence. Both sense and antisense sequences can exist on different parts of the same strand of DNA (i.e. both strands can contain both sense and antisense sequences). In both prokaryotes and eukaryotes, antisense RNA sequences are produced, but the functions of these RNAs are not entirely clear.<ref>{{cite journal | vauthors = Hüttenhofer A, Schattner P, Polacek N | title = Non-coding RNAs: hope or hype? | journal = Trends in Genetics | volume = 21 | issue = 5 | pages = 289–97 | date = May 2005 | pmid = 15851066 | doi = 10.1016/j.tig.2005.03.007 }}</ref> One proposal is that antisense RNAs are involved in regulating ] through RNA-RNA base pairing.<ref>{{cite journal | vauthors = Munroe SH | title = Diversity of antisense regulation in eukaryotes: multiple mechanisms, emerging patterns | journal = Journal of Cellular Biochemistry | volume = 93 | issue = 4 | pages = 664–71 | date = November 2004 | pmid = 15389973 | doi = 10.1002/jcb.20252 | s2cid = 23748148 }}</ref>
DNA exists in several possible conformations. The conformations so far identified are: A-DNA, B-DNA, C-DNA, D-DNA<ref name=Hayashi2005>{{cite journal | author = Hayashi G, Hagihara M, Nakatani K | title = Application of L-DNA as a molecular tag | journal = Nucleic Acids Symp Ser (Oxf) | volume = 49 | pages = 261-262 | year = 2005 | id = PMID 17150733}}</ref>, E-DNA<ref name=Vargason2000>{{cite journal | author = Vargason JM, Eichman BF, Ho PS | title = The extended and eccentric E-DNA structure induced by cytosine methylation or bromination | journal = Nature Structural Biology | volume = 7 | pages = 758-761 | year = 2000 | id = PMID 10966645}}</ref>, H-DNA<ref name=Wang2006>{{cite journal | author = Wang G, Vasquez KM | title = Non-B DNA structure-induced genetic instability | journal = Mutat Res | volume = 598 | issue = 1-2 | pages = 103-119 | year = 2006 | id = PMID 16516932}}</ref>, L-DNA<ref name=Hayashi2005>{{cite journal | author = Hayashi G, Hagihara M, Nakatani K | title = Application of L-DNA as a molecular tag | journal = Nucleic Acids Symp Ser (Oxf) | volume = 49 | pages = 261-262 | year = 2005 | id = PMID 17150733}}</ref>, and ].<ref name=Ghosh/><ref>{{cite journal | author = Palecek E | title = Local supercoil-stabilized DNA structures | journal = Crit Rev Biochem Mol Biol | volume = 26 | issue = 2 | pages = 151-226 | year = 1991 | id = PMID 1914495}}</ref> However, only A-DNA, B-DNA, and Z-DNA are believed to be found in nature. Which conformation DNA adopts depends on the sequence of the DNA, the amount and direction of supercoiling, chemical modifications of the bases and also solution conditions, such as the concentration of metal ions and ]s.<ref>{{cite journal | author = Basu H, Feuerstein B, Zarling D, Shafer R, Marton L | title = Recognition of Z-RNA and Z-DNA determinants by polyamines in solution: experimental and theoretical studies | journal = J Biomol Struct Dyn | volume = 6 | issue = 2 | pages = 299-309 | year = 1988 | id = PMID 2482766}}</ref> Of these three conformations, the "B" form described above is most common under the conditions found in cells. The two alternative double-helical forms of DNA differ in their geometry and dimensions.


A few DNA sequences in prokaryotes and eukaryotes, and more in ]s and ]es, blur the distinction between sense and antisense strands by having ]s.<ref>{{cite journal | vauthors = Makalowska I, Lin CF, Makalowski W | title = Overlapping genes in vertebrate genomes | journal = Computational Biology and Chemistry | volume = 29 | issue = 1 | pages = 1–12 | date = February 2005 | pmid = 15680581 | doi = 10.1016/j.compbiolchem.2004.12.006 }}</ref> In these cases, some DNA sequences do double duty, encoding one protein when read along one strand, and a second protein when read in the opposite direction along the other strand. In ], this overlap may be involved in the regulation of gene transcription,<ref>{{cite journal | vauthors = Johnson ZI, Chisholm SW | title = Properties of overlapping genes are conserved across microbial genomes | journal = Genome Research | volume = 14 | issue = 11 | pages = 2268–72 | date = November 2004 | pmid = 15520290 | pmc = 525685 | doi = 10.1101/gr.2433104 }}</ref> while in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome.<ref>{{cite journal | vauthors = Lamb RA, Horvath CM | title = Diversity of coding strategies in influenza viruses | journal = Trends in Genetics | volume = 7 | issue = 8 | pages = 261–66 | date = August 1991 | pmid = 1771674 | doi = 10.1016/0168-9525(91)90326-L | pmc = 7173306 }}</ref>
The A form is a wider right-handed spiral, with a shallow and wide minor groove and a narrower and deeper major groove. The A form occurs under non-physiological conditions in dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands.<ref>{{cite journal | author = Wahl M, Sundaralingam M | title = Crystal structures of A-DNA duplexes | journal = Biopolymers | volume = 44 | issue = 1 | pages = 45-63 | year = 1997 | id = PMID 9097733}}</ref> Segments of DNA where the bases have been ] may undergo a larger change in conformation and adopt the ]. Here, the strands turn about the helical axis in a left-handed spiral, a mirror image of the more common B form.<ref>{{cite journal | author = Rothenburg S, Koch-Nolte F, Haag F | title = DNA methylation and Z-DNA formation as mediators of quantitative differences in the expression of alleles | journal = Immunol Rev | volume = 184 | issue = | pages = 286-98 | year = | id = PMID 12086319}}</ref>


=== Supercoiling ===
] repeats.<ref>Created from </ref>]]
{{further|DNA supercoil}}


DNA can be twisted like a rope in a process called ]ing. With DNA in its "relaxed" state, a strand usually circles the axis of the double helix once every 10.4 base pairs, but if the DNA is twisted the strands become more tightly or more loosely wound.<ref>{{cite journal | vauthors = Benham CJ, Mielke SP | s2cid = 1427671 | title = DNA mechanics | journal = Annual Review of Biomedical Engineering | volume = 7 | pages = 21–53 | year = 2005 | pmid = 16004565 | doi = 10.1146/annurev.bioeng.6.062403.132016 | url = http://pdfs.semanticscholar.org/ab63/d57290ebf9bc3536fd3f2257a2b509076fc1.pdf | archive-url = https://web.archive.org/web/20190301225243/http://pdfs.semanticscholar.org/ab63/d57290ebf9bc3536fd3f2257a2b509076fc1.pdf | url-status = dead | archive-date = 1 March 2019 }}</ref> If the DNA is twisted in the direction of the helix, this is positive supercoiling, and the bases are held more tightly together. If they are twisted in the opposite direction, this is negative supercoiling, and the bases come apart more easily. In nature, most DNA has slight negative supercoiling that is introduced by ]s called ]s.<ref name=Champoux>{{cite journal | vauthors = Champoux JJ | s2cid = 18144189 | title = DNA topoisomerases: structure, function, and mechanism | journal = Annual Review of Biochemistry | volume = 70 | pages = 369–413 | year = 2001 | pmid = 11395412 | doi = 10.1146/annurev.biochem.70.1.369 }}</ref> These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as ] and ].<ref name=Wang>{{cite journal | vauthors = Wang JC | title = Cellular roles of DNA topoisomerases: a molecular perspective | journal = Nature Reviews Molecular Cell Biology | volume = 3 | issue = 6 | pages = 430–40 | date = June 2002 | pmid = 12042765 | doi = 10.1038/nrm831 | s2cid = 205496065 }}</ref>
===Quadruplex structures===
At the ends of the linear ]s are specialized regions of DNA called ]s. The main function of these regions is to allow the cell to replicate chromosome ends using the enzyme ], as normal ]s working on the ] cannot copy the extreme 3' ends of their DNA templates.<ref name=Greider>{{cite journal | author = Greider C, Blackburn E | title = Identification of a specific telomere terminal transferase activity in Tetrahymena extracts | journal = Cell | volume = 43 | issue = 2 Pt 1 | pages = 405-13 | year = 1985 | id = PMID 3907856}}</ref> If a chromosome lacked telomeres it would become shorter each time it was replicated. These specialized chromosome caps also help protect the DNA ends from ]s and stop the ] systems in the cell from treating them as damage to be corrected.<ref name=Nugent>{{cite journal | author = Nugent C, Lundblad V | title = The telomerase reverse transcriptase: components and regulation | url=http://www.genesdev.org/cgi/content/full/12/8/1073 | journal = Genes Dev | volume = 12 | issue = 8 | pages = 1073-85 | year = 1998 | id = PMID 9553037}}</ref> In human cells, telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence.<ref>{{cite journal | author = Wright W, Tesmer V, Huffman K, Levene S, Shay J | title = Normal human chromosomes have long G-rich telomeric overhangs at one end | url=http://www.genesdev.org/cgi/content/full/11/21/2801#B34 | journal = Genes Dev | volume = 11 | issue = 21 | pages = 2801-9 | year = 1997 | id = PMID 9353250}}</ref>


=== Alternative DNA structures ===
These guanine-rich sequences may stabilise chromosome ends by forming very unusual quadruplex structures. Here, four guanine bases form a flat plate, through hydrogen bonding, and these flat four-base units then stack on top of each other, to form a stable quadruplex.<ref name=Burge>{{cite journal | author = Burge S, Parkinson G, Hazel P, Todd A, Neidle S | title = Quadruplex DNA: sequence, topology and structure | url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17012276 | journal = Nucleic Acids Res | volume = 34 | issue = 19 | pages = 5402-15 | year = 2006 | id = PMID 17012276}}</ref> These structures are often stabilized by ] of a metal ion in the centre of each four-base unit. The structure shown to the left is of a quadruplex formed by a DNA sequence containing four consecutive human telomere repeats. The single DNA strand forms a loop, with the sets of four bases stacking in a central quadruplex three plates deep. In the space at the centre of the stacked bases are three chelated potassium ions.<ref>{{cite journal | author = Parkinson G, Lee M, Neidle S | title = Crystal structure of parallel quadruplexes from human telomeric DNA | journal = Nature | volume = 417 | issue = 6891 | pages = 876-80 | year = 2002 | id = PMID 12050675}}</ref> Other structures can also be formed and the central set of four bases can come from either one folded strand, or several different parallel strands.
{{further|Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid|Molecular models of DNA|DNA structure}}
], ] and ]]]


DNA exists in many possible ] that include ], ], and ] forms, although only B-DNA and Z-DNA have been directly observed in functional organisms.<ref name=Ghosh /> The conformation that DNA adopts depends on the hydration level, DNA sequence, the amount and direction of supercoiling, chemical modifications of the bases, the type and concentration of metal ]s, and the presence of ]s in solution.<ref>{{cite journal | vauthors = Basu HS, Feuerstein BG, Zarling DA, Shafer RH, Marton LJ | title = Recognition of Z-RNA and Z-DNA determinants by polyamines in solution: experimental and theoretical studies | journal = Journal of Biomolecular Structure & Dynamics | volume = 6 | issue = 2 | pages = 299–309 | date = October 1988 | pmid = 2482766 | doi = 10.1080/07391102.1988.10507714 }}</ref>
In addition to these stacked structures, telomeres also form large loop structures called telomere loops, or T-loops. Here, the single-stranded DNA curls around in a circle stabilized by telomere-binding proteins.<ref>{{cite journal | author = Griffith J, Comeau L, Rosenfield S, Stansel R, Bianchi A, Moss H, de Lange T | title = Mammalian telomeres end in a large duplex loop | journal = Cell | volume = 97 | issue = 4 | pages = 503-14 | year = 1999 | id = PMID 10338214}}</ref> The very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere strand disrupting the double-helical DNA and base pairing to one of the two strands. This triple-stranded structure is called a displacement loop or D-loop.<ref name=Burge/>


The first published reports of A-DNA ]—and also B-DNA—used analyses based on ]s that provided only a limited amount of structural information for oriented fibers of DNA.<ref>
==Chemical modifications==
* {{cite journal |vauthors=Franklin RE, Gosling RG |title=The Structure of Sodium Thymonucleate Fibres I. The Influence of Water Content |journal=Acta Crystallogr |volume=6 |issue=8–9 |pages=673–77 |date=6 March 1953 |doi=10.1107/S0365110X53001939 |bibcode=1953AcCry...6..673F |url=http://journals.iucr.org/q/issues/1953/08-09/00/a00979/a00979.pdf |url-status=live |archive-url=https://web.archive.org/web/20160109043915/http://journals.iucr.org/q/issues/1953/08-09/00/a00979/a00979.pdf |archive-date=9 January 2016 |doi-access=free }}
===Regulatory base modifications===
* {{cite journal |vauthors=Franklin RE, Gosling RG |title=The structure of sodium thymonucleate fibres. II. The cylindrically symmetrical Patterson function |journal=Acta Crystallogr |volume=6 |issue=8–9 |pages=678–85 |year=1953|doi=10.1107/S0365110X53001940|bibcode=1953AcCry...6..678F |url=http://journals.iucr.org/q/issues/1953/08-09/00/a00980/a00980.pdf |archive-url=https://web.archive.org/web/20170629084321/http://journals.iucr.org/q/issues/1953/08-09/00/a00980/a00980.pdf |archive-date=2017-06-29 |url-status=live |doi-access=free }}</ref><ref name=NatFranGos>{{cite journal | vauthors = Franklin RE, Gosling RG | title = Molecular configuration in sodium thymonucleate | journal = Nature | volume = 171 | issue = 4356 | pages = 740–41 | date = April 1953 | pmid = 13054694 | doi = 10.1038/171740a0 | url = http://www.nature.com/nature/dna50/franklingosling.pdf | bibcode = 1953Natur.171..740F | s2cid = 4268222 | url-status=live | archive-url = https://web.archive.org/web/20110103160712/http://www.nature.com/nature/dna50/franklingosling.pdf | archive-date = 3 January 2011 | df = dmy-all }}</ref> An alternative analysis was proposed by Wilkins ''et al.'' in 1953 for the '']'' B-DNA X-ray diffraction-scattering patterns of highly hydrated DNA fibers in terms of squares of ]s.<ref name=NatWilk>{{cite journal | vauthors = Wilkins MH, Stokes AR, Wilson HR | title = Molecular structure of deoxypentose nucleic acids | journal = Nature | volume = 171 | issue = 4356 | pages = 738–40 | date = April 1953 | pmid = 13054693 | doi = 10.1038/171738a0 | url = http://www.nature.com/nature/dna50/wilkins.pdf | bibcode = 1953Natur.171..738W | s2cid = 4280080 | url-status=live | archive-url = https://web.archive.org/web/20110513234223/http://www.nature.com/nature/dna50/wilkins.pdf | archive-date = 13 May 2011 | df = dmy-all }}</ref> In the same journal, ] and ] presented their ] analysis of the DNA X-ray diffraction patterns to suggest that the structure was a double helix.<ref name="Watson-1953" />
{{further|]}}
The expression of genes is influenced by modifications of the bases in DNA. In humans, the most common base modification is ] ] to produce ]. This modification reduces gene expression and is important in ].<ref>{{cite journal | author = Klose R, Bird A | title = Genomic DNA methylation: the mark and its mediators | journal = Trends Biochem Sci | volume = 31 | issue = 2 | pages = 89-97 | year = 2006 | id = PMID 16403636}}</ref> The level of methylation varies between organisms, with '']'' lacking cytosine methylation, while vertebrates show high levels, with up to 1% of their DNA being 5-methylcytosine.<ref>{{cite journal | author = Bird A | title = DNA methylation patterns and epigenetic memory | journal = Genes Dev | volume = 16 | issue = 1 | pages = 6-21 | year = 2002 | id = PMID 11782440}}</ref> Unfortunately, the spontaneous ] of 5-methylcytosine produces thymine and methylated cytosines are therefore mutation hotspots.<ref>{{cite journal | author = Walsh C, Xu G | title = Cytosine methylation and DNA repair | journal = Curr Top Microbiol Immunol | volume = 301 | issue = | pages = 283-315 | year = | id = PMID 16570853}}</ref> Other base modifications include adenine methylation in bacteria and the ] of uracil to produce the "J-base" in ]s.<ref>{{cite journal | author = Ratel D, Ravanat J, Berger F, Wion D | title = N6-methyladenine: the other methylated base of DNA | journal = Bioessays | volume = 28 | issue = 3 | pages = 309-15 | year = 2006 | id = PMID 16479578}}</ref><ref>{{cite journal | author = Gommers-Ampt J, Van Leeuwen F, de Beer A, Vliegenthart J, Dizdaroglu M, Kowalak J, Crain P, Borst P | title = beta-D-glucosyl-hydroxymethyluracil: a novel modified base present in the DNA of the parasitic protozoan T. brucei | journal = Cell | volume = 75 | issue = 6 | pages = 1129-36 | year = 1993 | id = PMID 8261512}}</ref>


Although the ''B-DNA form'' is most common under the conditions found in cells,<ref>{{cite journal | vauthors = Leslie AG, Arnott S, Chandrasekaran R, Ratliff RL | title = Polymorphism of DNA double helices | journal = Journal of Molecular Biology | volume = 143 | issue = 1 | pages = 49–72 | date = October 1980 | pmid = 7441761 | doi = 10.1016/0022-2836(80)90124-2 }}</ref> it is not a well-defined conformation but a family of related DNA conformations<ref>{{cite journal|vauthors=Baianu IC|s2cid=189888972|year=1980|title=Structural Order and Partial Disorder in Biological systems|url=http://cogprints.org/3822/|journal=Bull. Math. Biol.|volume=42|issue=4|pages=137–41|doi=10.1007/BF02462372}}</ref> that occur at the high hydration levels present in cells. Their corresponding X-ray diffraction and scattering patterns are characteristic of molecular ] with a significant degree of disorder.<ref>{{cite book | vauthors = Hosemann R, Bagchi RN | title = Direct analysis of diffraction by matter | publisher = North-Holland Publishers | location = Amsterdam&nbsp;– New York | year = 1962 }}</ref><ref>{{cite journal|vauthors=Baianu IC|title=X-ray scattering by partially disordered membrane systems|journal=Acta Crystallogr A|volume=34|issue=5|pages=751–53|year=1978|doi=10.1107/S0567739478001540|bibcode=1978AcCrA..34..751B|url=http://journals.iucr.org/a/issues/1978/05/00/a15615/a15615.pdf|access-date=29 August 2019|archive-date=14 March 2020|archive-url=https://web.archive.org/web/20200314050140/http://journals.iucr.org/a/issues/1978/05/00/a15615/a15615.pdf|url-status=dead}}</ref>
===DNA damage===
{{further|]}}


Compared to B-DNA, the A-DNA form is a wider ] spiral, with a shallow, wide minor groove and a narrower, deeper major groove. The A form occurs under non-physiological conditions in partly dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands, and in enzyme-DNA complexes.<ref>{{cite journal | vauthors = Wahl MC, Sundaralingam M | title = Crystal structures of A-DNA duplexes | journal = Biopolymers | volume = 44 | issue = 1 | pages = 45–63 | year = 1997 | pmid = 9097733 | doi = 10.1002/(SICI)1097-0282(1997)44:1<45::AID-BIP4>3.0.CO;2-# }}</ref><ref>{{cite journal | vauthors = Lu XJ, Shakked Z, Olson WK | title = A-form conformational motifs in ligand-bound DNA structures | journal = Journal of Molecular Biology | volume = 300 | issue = 4 | pages = 819–40 | date = July 2000 | pmid = 10891271 | doi = 10.1006/jmbi.2000.3690 }}</ref> Segments of DNA where the bases have been chemically modified by ] may undergo a larger change in conformation and adopt the ]. Here, the strands turn about the helical axis in a left-handed spiral, the opposite of the more common B form.<ref>{{cite journal | vauthors = Rothenburg S, Koch-Nolte F, Haag F | title = DNA methylation and Z-DNA formation as mediators of quantitative differences in the expression of alleles | journal = Immunological Reviews | volume = 184 | pages = 286–98 | date = December 2001 | pmid = 12086319 | doi = 10.1034/j.1600-065x.2001.1840125.x | s2cid = 20589136 }}</ref> These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in the regulation of transcription.<ref>{{cite journal | vauthors = Oh DB, Kim YG, Rich A | title = Z-DNA-binding proteins can act as potent effectors of gene expression in vivo | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 26 | pages = 16666–71 | date = December 2002 | pmid = 12486233 | pmc = 139201 | doi = 10.1073/pnas.262672699 | bibcode = 2002PNAS...9916666O | doi-access = free }}</ref>
], the major mutagen in ], in an adduct to DNA.<ref>Created from </ref>]]
DNA can be damaged by many different sorts of ]s. These include ]s, ]s and also high-energy ] such as ] and ]. The type of DNA damage produced depends on the type of mutagen. For example, UV light mostly damages DNA by producing ]s, which are cross-links between adjacent pyrimidine bases in a DNA strand.<ref>{{cite journal | author = Douki T, Reynaud-Angelin A, Cadet J, Sage E | title = Bipyrimidine photoproducts rather than oxidative lesions are the main type of DNA damage involved in the genotoxic effect of solar UVA radiation | journal = Biochemistry | volume = 42 | issue = 30 | pages = 9221-6 | year = 2003 | id = PMID 12885257}},</ref> On the other hand, oxidants such as ]s or ] produce multiple forms of damage, including base modifications, particularly of guanosine, as well as double-strand breaks.<ref>{{cite journal | author = Cadet J, Delatour T, Douki T, Gasparutto D, Pouget J, Ravanat J, Sauvaigo S | title = Hydroxyl radicals and DNA base damage | journal = Mutat Res | volume = 424 | issue = 1-2 | pages = 9-21 | year = 1999 | id = PMID 10064846}}</ref> It has been estimated that in each human cell, about 500 bases suffer oxidative damage per day.<ref>{{cite journal | author = Shigenaga M, Gimeno C, Ames B | title = Urinary 8-hydroxy-2'-deoxyguanosine as a biological marker of in vivo oxidative DNA damage | url=http://www.pnas.org/cgi/reprint/86/24/9697 | journal = Proc Natl Acad Sci U S A | volume = 86 | issue = 24 | pages = 9697-701 | year = 1989 | id = PMID 2602371}}</ref><ref>{{cite journal | author = Cathcart R, Schwiers E, Saul R, Ames B | title = Thymine glycol and thymidine glycol in human and rat urine: a possible assay for oxidative DNA damage | url=http://www.pnas.org/cgi/reprint/81/18/5633.pdf | journal = Proc Natl Acad Sci U S A | volume = 81 | issue = 18 | pages = 5633-7 | year = 1984 | id = PMID 6592579}}</ref> Of these oxidative lesions, the most damaging are double-strand breaks, as they can produce ]s, insertions and deletions from the DNA sequence, as well as ]s.<ref>{{cite journal | author = Valerie K, Povirk L | title = Regulation and mechanisms of mammalian double-strand break repair | journal = Oncogene | volume = 22 | issue = 37 | pages = 5792-812 | year = 2003 | id = PMID 12947387}}</ref>


=== Alternative DNA chemistry ===
Many mutagens ] into the space between two adjacent ]s. These molecules are mostly polycyclic, ], and planar molecules and include ], ], ], ] and ]. DNA intercalators are used in ] to inhibit DNA replication in rapidly-growing cancer cells.<ref>{{cite journal | author = Braña M, Cacho M, Gradillas A, de Pascual-Teresa B, Ramos A | title = Intercalators as anticancer drugs | journal = Curr Pharm Des | volume = 7 | issue = 17 | pages = 1745-80 | year = 2001 | id = PMID 11562309}}</ref> In order for an intercalator to fit between base pairs, the bases must separate, distorting the DNA strand by unwinding of the double helix. These structural modifications inhibit ] and ] processes, causing both toxicity and mutations. As a result, DNA intercalators are often ]s, with ], ]s, ] and ] being well-known examples.<ref>{{cite journal | author = Ferguson L, Denny W | title = The genetic toxicology of acridines | journal = Mutat Res | volume = 258 | issue = 2 | pages = 123-60 | year = 1991 | id = PMID 1881402}}</ref><ref>{{cite journal | author = Jeffrey A | title = DNA modification by chemical carcinogens | journal = Pharmacol Ther | volume = 28 | issue = 2 | pages = 237-72 | year = 1985 | id = PMID 3936066}}</ref>
{{further|hypothetical types of biochemistry}}
For many years, ] have proposed the existence of a ], a postulated microbial ] of Earth that uses radically different biochemical and molecular processes than currently known life. One of the proposals was the existence of lifeforms that use ]. A report in 2010 of the possibility in the ] ] was announced,<ref name='arsenic extremophile'>{{cite news | vauthors = Palmer J |title=Arsenic-loving bacteria may help in hunt for alien life |date=2 December 2010 |url=https://www.bbc.co.uk/news/science-environment-11886943 |work=BBC News |access-date=2 December 2010 |url-status=live |archive-url=https://web.archive.org/web/20101203045804/http://www.bbc.co.uk/news/science-environment-11886943 |archive-date=3 December 2010 }}</ref><ref name="Space">{{cite news | vauthors = Bortman H |title=Arsenic-Eating Bacteria Opens New Possibilities for Alien Life |date=2 December 2010 |url=http://www.space.com/scienceastronomy/arsenic-bacteria-alien-life-101202.html |website=Space.com |access-date=2 December 2010 |url-status=live |archive-url=https://web.archive.org/web/20101204235915/http://www.space.com/scienceastronomy/arsenic-bacteria-alien-life-101202.html |archive-date=4 December 2010 }}</ref> though the research was disputed,<ref name="Space" /><ref>{{cite journal | vauthors = Katsnelson A |title=Arsenic-eating microbe may redefine chemistry of life |date=2 December 2010 |url=http://www.nature.com/news/2010/101202/full/news.2010.645.html |journal=Nature News |doi=10.1038/news.2010.645 |url-status=live |archive-url=https://web.archive.org/web/20120212155007/http://www.nature.com/news/2010/101202/full/news.2010.645.html |archive-date=12 February 2012 }}</ref> and evidence suggests the bacterium actively prevents the incorporation of arsenic into the DNA backbone and other biomolecules.<ref name="Nature">{{cite journal | vauthors = Cressey D |s2cid=87341731 |title='Arsenic-life' Bacterium Prefers Phosphorus after all |date=3 October 2012 |journal=Nature News |doi=10.1038/nature.2012.11520}}</ref>


=== Quadruplex structures ===
==Overview of biological functions==
{{further|G-quadruplex}}
DNA contains the genetic ] that allows living things to function, grow and reproduce. This information is held in the ] of pieces of DNA called ]s. Genetic information in genes is transmitted through complementary base pairing. For example, when a cell uses the information in a gene, the DNA sequence is copied into a complementary RNA sequence in a process called transcription. Usually, this RNA copy is then used to make a matching protein sequence in a process called translation. Alternatively, a cell may simply copy its genetic information in a process called DNA replication. The details of these functions are covered in other articles, here we focus on the interactions that happen in these processes between DNA and other molecules.
] repeats. The looped conformation of the DNA backbone is very different from the typical DNA helix. The green spheres in the center represent potassium ions.<ref>{{Cite web|title=Structure and packing of human telomeric DNA|url=http://ndbserver.rutgers.edu/service/ndb/atlas/summary?searchTarget=UD0017|access-date=2023-05-18|website=ndbserver.rutgers.edu}}</ref>]]
] producing a mRNA (green) from a DNA template (red and blue). The protein is shown as a purple ribbon.<ref>Created from </ref>]]
===Transcription and translation===
{{further|], ], ]}}
A gene is a sequence of DNA that contains genetic information and can influence the ] of an organism. Within a gene, the sequence of bases along a DNA strand defines a ] sequence which then defines a protein sequence. The relationship between the nucleotide sequences of genes and the ] sequences of proteins is determined by the rules of ], known collectively as the ]. The genetic code consists of three-letter 'words' called ''codons'' formed from a sequence of three nucleotides (e.g. ACT, CAG, TTT). In transcription, the codons of a gene are copied into ] by ]. This RNA copy is then decoded by a ] that reads the RNA sequence by base-pairing the messenger RNA to ], which carries amino acids. Since there are 4 bases in 3-letter combinations, there are 64 possible codons (<math>4^3</math> combinations). These encode the twenty ]. Most amino acids, therefore, have more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region, these are the TAA, TGA and TAG codons.


At the ends of the linear chromosomes are specialized regions of DNA called ]s. The main function of these regions is to allow the cell to replicate chromosome ends using the enzyme ], as the enzymes that normally replicate DNA cannot copy the extreme 3′ ends of chromosomes.<ref name=Greider>{{cite journal | vauthors = Greider CW, Blackburn EH | title = Identification of a specific telomere terminal transferase activity in Tetrahymena extracts | journal = Cell | volume = 43 | issue = 2 Pt 1 | pages = 405–13 | date = December 1985 | pmid = 3907856 | doi = 10.1016/0092-8674(85)90170-9 | doi-access = free }}</ref> These specialized chromosome caps also help protect the DNA ends, and stop the ] systems in the cell from treating them as damage to be corrected.<ref name=Nugent>{{cite journal | vauthors = Nugent CI, Lundblad V | title = The telomerase reverse transcriptase: components and regulation | journal = Genes & Development | volume = 12 | issue = 8 | pages = 1073–85 | date = April 1998 | pmid = 9553037 | doi = 10.1101/gad.12.8.1073 | doi-access = free }}</ref> In ], telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence.<ref>{{cite journal | vauthors = Wright WE, Tesmer VM, Huffman KE, Levene SD, Shay JW | title = Normal human chromosomes have long G-rich telomeric overhangs at one end | journal = Genes & Development | volume = 11 | issue = 21 | pages = 2801–09 | date = November 1997 | pmid = 9353250 | pmc = 316649 | doi = 10.1101/gad.11.21.2801 }}</ref>
]. Next, ] (green) produces the ] copy (red). A DNA polymerase I molecule (green) binds to the ]. This enzyme makes discontinuous segments (called ]s) before ] (violet) joins them together.]]


These guanine-rich sequences may stabilize chromosome ends by forming structures of stacked sets of four-base units, rather than the usual base pairs found in other DNA molecules. Here, four guanine bases, known as a ], form a flat plate. These flat four-base units then stack on top of each other to form a stable ] structure.<ref name=Burge>{{cite journal | vauthors = Burge S, Parkinson GN, Hazel P, Todd AK, Neidle S | title = Quadruplex DNA: sequence, topology and structure | journal = Nucleic Acids Research | volume = 34 | issue = 19 | pages = 5402–15 | year = 2006 | pmid = 17012276 | pmc = 1636468 | doi = 10.1093/nar/gkl655 }}</ref> These structures are stabilized by hydrogen bonding between the edges of the bases and ] of a metal ion in the centre of each four-base unit.<ref>{{cite journal | vauthors = Parkinson GN, Lee MP, Neidle S | title = Crystal structure of parallel quadruplexes from human telomeric DNA | journal = Nature | volume = 417 | issue = 6891 | pages = 876–80 | date = June 2002 | pmid = 12050675 | doi = 10.1038/nature755 | bibcode = 2002Natur.417..876P | s2cid = 4422211 }}</ref> Other structures can also be formed, with the central set of four bases coming from either a single strand folded around the bases, or several different parallel strands, each contributing one base to the central structure.
===Replication===
{{further|]}}


In addition to these stacked structures, telomeres also form large loop structures called telomere loops, or T-loops. Here, the single-stranded DNA curls around in a long circle stabilized by telomere-binding proteins.<ref>{{cite journal | vauthors = Griffith JD, Comeau L, Rosenfield S, Stansel RM, Bianchi A, Moss H, de Lange T | s2cid = 721901 | title = Mammalian telomeres end in a large duplex loop | journal = Cell | volume = 97 | issue = 4 | pages = 503–14 | date = May 1999 | pmid = 10338214 | doi = 10.1016/S0092-8674(00)80760-6 | citeseerx = 10.1.1.335.2649 }}</ref> At the very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere strand disrupting the double-helical DNA and base pairing to one of the two strands. This ] structure is called a displacement loop or ].<ref name=Burge />
] is essential for an organism to grow, but when a cell divides it must replicate the DNA in its genome so that the two daughter cells have the same genetic information as their parent. The double-stranded structure of DNA provides a simple mechanism for ]. Here, the two strands are separated and then each strand's complementary DNA sequence is recreated by an enzyme called ]. This enzyme makes the complementary strand by finding the correct base through complementary base pairing, and bonding it onto the original strand. As DNA polymerases can only extend a DNA strand in a 5ˈ to 3ˈ direction, different mechanisms are used to copy the antiparallel strands of the double helix.<ref>{{cite journal | author = Albà M | title = Replicative DNA polymerases | url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=11178285 | journal = Genome Biol | volume = 2 | issue = 1 | pages = REVIEWS3002 | year = 2001 | id = PMID 11178285}}</ref> In this way, the base on the old strand dictates which base appears on the new strand, and the cell ends up with a perfect copy of its DNA.


==Genes and genomes== === Branched DNA ===
{{further|], ], ]}} {{further|Branched DNA|DNA nanotechnology}}
<div class="thumb tright" style="background:#f9f9f9; border:1px solid #ccc; margin:0.5em;">
DNA is located in the ] of eukaryotes, as well as small amounts in ] and ]s. In prokaryotes, the DNA is held within an irregularly shaped body in the cytoplasm called the ].<ref>{{cite journal | author = Thanbichler M, Wang S, Shapiro L | title = The bacterial nucleoid: a highly organized and dynamic structure | journal = J Cell Biochem | volume = 96 | issue = 3 | pages = 506–21 | year = 2005 | id = PMID 15988757}}</ref> The DNA is usually in linear ]s in eukaryotes, and circular chromosomes in prokaryotes. In the ], there is approximately 3 billion base pairs of DNA arranged into 46 chromosomes.<ref>{{cite journal | author = Venter J, ''et. al.'' | title = The sequence of the human genome | journal = Science | volume = 291 | issue = 5507 | pages = 1304-51 | year = 2001 | id = PMID 11181995}}</ref> The genetic information in a genome is held within ]s. A gene is a unit of heredity and is a region of DNA that influences a particular characteristic in an organism. Genes contain an ] that can be transcribed, as well as ]s such as ]s and ], which control the expression of the open reading frame.
{| border="0" cellpadding="2" cellspacing="0" style="width:200px; font-size:85%; border:1px solid #ccc; margin:0.3em;"
|]
|]
|-
|align=center|Single branch
|align=center|Multiple branches
|}
<div style="border: none; width:200px;font-size: 90%;"><div class="thumbcaption">] can form networks containing multiple branches.</div></div></div>
In DNA, ] occurs when non-complementary regions exist at the end of an otherwise complementary double-strand of DNA. However, branched DNA can occur if a third strand of DNA is introduced and contains adjoining regions able to hybridize with the frayed regions of the pre-existing double-strand. Although the simplest example of branched DNA involves only three strands of DNA, complexes involving additional strands and multiple branches are also possible.<ref>{{cite journal | vauthors = Seeman NC | title = DNA enables nanoscale control of the structure of matter | journal = Quarterly Reviews of Biophysics | volume = 38 | issue = 4 | pages = 363–71 | date = November 2005 | pmid = 16515737 | pmc = 3478329 | doi = 10.1017/S0033583505004087 }}</ref> Branched DNA can be used in ] to construct geometric shapes, see the section on ] below.


=== Artificial bases ===
In many ], only a small fraction of the total sequence of the ] encodes protein. For example, only about 1.5% of the ] consists of protein-coding ], with over 50% of human DNA consisting of non-coding ].<ref>{{cite journal | author = Wolfsberg T, McEntyre J, Schuler G | title = Guide to the draft human genome | journal = Nature | volume = 409 | issue = 6822 | pages = 824-6 | year = 2001 | id = PMID 11236998}}</ref> The reasons for the presence of so much ] in ] genomes and the extraordinary differences in ], or '']'', among species represent a long-standing puzzle known as the "]".<ref>{{cite journal | author = Gregory T | title = The C-value enigma in plants and animals: a review of parallels and an appeal for partnership | url=http://aob.oxfordjournals.org/cgi/content/full/95/1/133 | journal = Ann Bot (Lond) | volume = 95 | issue = 1 | pages = 133-46 | year = 2005 | id = PMID 15596463}}</ref>
{{Main|Nucleic acid analogue}}


Several artificial nucleobases have been synthesized, and successfully incorporated in the eight-base DNA analogue named ]. Dubbed S, B, P, and Z, these artificial bases are capable of bonding with each other in a predictable way (S–B and P–Z), maintain the double helix structure of DNA, and be transcribed to RNA. Their existence could be seen as an indication that there is nothing special about the four natural nucleobases that evolved on Earth.<ref>{{cite journal | vauthors = Warren M |title=Four new DNA letters double life's alphabet | journal = Nature |date=21 February 2019 | doi = 10.1038/d41586-019-00650-8 | pmid = 30809059 | volume=566 | issue = 7745 | page=436| doi-access = free | bibcode = 2019Natur.566..436W }}</ref><ref>{{cite journal| vauthors = Hoshika S, Leal NA, Kim MJ, Kim MS, Karalkar NB, Kim HJ, Bates AM, Watkins NE, SantaLucia HA, Meyer AJ, DasGupta S, Piccirilli JA, Ellington AD, SantaLucia J, Georgiadis MM, Benner SA | display-authors = 6 |title=Hachimoji DNA and RNA: A genetic system with eight building blocks (paywall)|journal=] |volume=363 |issue=6429 |pages=884–887 |date=22 February 2019 | doi = 10.1126/science.aat0971 | pmid = 30792304 | pmc=6413494 | bibcode=2019Sci...363..884H}}</ref> On the other hand, DNA is tightly related to ] which does not only act as a transcript of DNA but also performs as molecular machines many tasks in cells. For this purpose it has to fold into a structure. It has been shown that to allow to create all possible structures at least four bases are required for the corresponding ],<ref>{{cite journal | vauthors = Burghardt B, Hartmann AK | title = RNA secondary structure design | journal = Physical Review E | volume = 75 | issue = 2 | pages = 021920 | date = February 2007 | doi = 10.1103/PhysRevE.75.021920 | pmid = 17358380 | url = https://link.aps.org/doi/10.1103/PhysRevE.75.021920| arxiv = physics/0609135 | bibcode = 2007PhRvE..75b1920B | s2cid = 17574854 }}</ref> while a higher number is also possible but this would be against the natural ].
Some non-coding DNA sequences play structural roles in chromosomes. ]s and ]s typically contain few genes, but are important for the function and stability of chromosomes.<ref name=Nugent/><ref>{{cite journal | author = Pidoux A, Allshire R | title = The role of heterochromatin in centromere function | url=http://www.journals.royalsoc.ac.uk/media/804t6y8vmh5utlb6ua5y/contributions/p/x/7/a/px7ahm740dq5ueuk.pdf | journal = Philos Trans R Soc Lond B Biol Sci | volume = 360 | issue = 1455 | pages = 569-79 | year = 2005 | id = PMID 15905142}}</ref> An abundant form of non-coding DNA in humans are ]s, which are copies of genes that have been disabled by mutation.<ref>{{cite journal | author = Harrison P, Hegyi H, Balasubramanian S, Luscombe N, Bertone P, Echols N, Johnson T, Gerstein M | title = Molecular fossils in the human genome: identification and analysis of the pseudogenes in chromosomes 21 and 22 | url=http://www.genome.org/cgi/content/full/12/2/272 | journal = Genome Res | volume = 12 | issue = 2 | pages = 272-80 | year = 2002 | id = PMID 11827946}}</ref> These sequences are usually just molecular fossils, although they can occasionally serve as raw genetic material for the creation of new genes through the process of ] and ].<ref>{{cite journal | author = Harrison P, Gerstein M | title = Studying genomes through the aeons: protein families, pseudogenes and proteome evolution | journal = J Mol Biol | volume = 318 | issue = 5 | pages = 1155-74 | year = 2002 | id = PMID 12083509}}</ref>


===Acidity===
==Interactions with proteins==
The phosphate groups of DNA give it similar ]ic properties to ] and it can be considered as a ]. It will be fully ionized at a normal cellular pH, releasing ]s which leave behind negative charges on the phosphate groups. These negative charges protect DNA from breakdown by ] by repelling ]s which could hydrolyze it.<ref name="Reusch">{{cite web | vauthors = Reusch W |title=Nucleic Acids |url=https://www2.chemistry.msu.edu/faculty/reusch/VirtTxtJml/nucacids.htm |publisher=Michigan State University |access-date=30 June 2022}}</ref>
All the functions of DNA depend on interactions with proteins. These protein interactions can either be non-specific, or the protein can only bind to a particular DNA sequence. Enzymes can also bind to DNA and of these, the polymerases that copy the DNA base sequence in transcription and DNA replication are particularly important.


===DNA-binding proteins=== ===Macroscopic appearance===
]
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Pure DNA extracted from cells forms white, stringy clumps.<ref>{{cite web |title=How To Extract DNA From Anything Living |url=https://learn.genetics.utah.edu/content/labs/extraction/howto/ |publisher=University of Utah |access-date=30 June 2022}}</ref>
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== Chemical modifications and altered DNA packaging ==

=== Base modifications and DNA packaging ===
{{further|DNA methylation|Chromatin remodeling}}
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<div style="border: none; width:260px;"><div class="thumbcaption">Interaction of DNA with ]s (shown in white, top). These proteins' basic amino acids (below left, blue) bind to the acidic phosphate groups on DNA (below right, red).</div></div></div> <div style="border: none; width:300px;font-size: 90%;"><div class="thumbcaption">Structure of cytosine with and without the 5-methyl group. ] converts 5-methylcytosine into thymine.</div></div></div>
The expression of genes is influenced by how the DNA is packaged in chromosomes, in a structure called ]. Base modifications can be involved in packaging, with regions that have low or no gene expression usually containing high levels of ] of ] bases. DNA packaging and its influence on gene expression can also occur by covalent modifications of the ] protein core around which DNA is wrapped in the chromatin structure or else by remodeling carried out by chromatin remodeling complexes (see ]). There is, further, ] between DNA methylation and histone modification, so they can coordinately affect chromatin and gene expression.<ref>{{cite journal | vauthors = Hu Q, Rosenfeld MG | title = Epigenetic regulation of human embryonic stem cells | journal = Frontiers in Genetics | volume = 3 | pages = 238 | year = 2012 | pmid = 23133442 | pmc = 3488762 | doi = 10.3389/fgene.2012.00238 | doi-access = free }}</ref>


Structural proteins that bind DNA are well-understood examples of non-specific DNA-protein interactions. Within chromosomes, DNA is held in complexes between DNA and structural proteins. These proteins organize the DNA into a compact structure called ]. In eukaryotes this structure involves DNA binding to a complex of small basic proteins called ]s, while in prokaryotes multiple types of proteins are involved.<ref>{{cite journal | author = Sandman K, Pereira S, Reeve J | title = Diversity of prokaryotic chromosomal proteins and the origin of the nucleosome | journal = Cell Mol Life Sci | volume = 54 | issue = 12 | pages = 1350-64 | year = 1998 | id = PMID 9893710}}</ref> The histones form a disk-shaped complex called a ], which contains two complete turns of double-stranded DNA wrapped around its surface. These non-specific interactions are formed through basic residues in the histones making ]s to the acidic sugar-phosphate backbone of the DNA, and are therefore largely independent of the base sequence.<ref>{{cite journal | author = Luger K, Mäder A, Richmond R, Sargent D, Richmond T | title = Crystal structure of the nucleosome core particle at 2.8 A resolution | journal = Nature | volume = 389 | issue = 6648 | pages = 251-60 | year = 1997 | id = PMID 9305837}}</ref> Chemical modifications of these basic amino acid residues include ], ] and ].<ref>{{cite journal | author = Jenuwein T, Allis C | title = Translating the histone code | journal = Science | volume = 293 | issue = 5532 | pages = 1074-80 | year = 2001 | id = PMID 11498575}}</ref> These chemical changes alter the strength of the interaction between the DNA and the histones, making the DNA more or less accessible to ]s and changing the rate of ].<ref>{{cite journal | author = Ito T | title = Nucleosome assembly and remodelling | journal = Curr Top Microbiol Immunol | volume = 274 | issue = | pages = 1-22 | year = | id = PMID 12596902}}</ref> Other non-specific DNA-binding proteins found in chromatin include the high-mobility group proteins, which bind preferentially to bent or distorted DNA.<ref>{{cite journal | author = Thomas J | title = HMG1 and 2: architectural DNA-binding proteins | journal = Biochem Soc Trans | volume = 29 | issue = Pt 4 | pages = 395-401 | year = 2001 | id = PMID 11497996}}</ref> These proteins are important in bending arrays of nucleosomes and arranging them into more complex chromatin structures.<ref>{{cite journal | author = Grosschedl R, Giese K, Pagel J | title = HMG domain proteins: architectural elements in the assembly of nucleoprotein structures | journal = Trends Genet | volume = 10 | issue = 3 | pages = 94-100 | year = 1994 | id = PMID 8178371}}</ref> For one example, cytosine methylation produces ], which is important for ] of chromosomes.<ref>{{cite journal | vauthors = Klose RJ, Bird AP | title = Genomic DNA methylation: the mark and its mediators | journal = Trends in Biochemical Sciences | volume = 31 | issue = 2 | pages = 89–97 | date = February 2006 | pmid = 16403636 | doi = 10.1016/j.tibs.2005.12.008 }}</ref> The average level of methylation varies between organisms—the worm '']'' lacks cytosine methylation, while ]s have higher levels, with up to 1% of their DNA containing 5-methylcytosine.<ref>{{cite journal | vauthors = Bird A | title = DNA methylation patterns and epigenetic memory | journal = Genes & Development | volume = 16 | issue = 1 | pages = 6–21 | date = January 2002 | pmid = 11782440 | doi = 10.1101/gad.947102 | doi-access = free }}</ref> Despite the importance of 5-methylcytosine, it can ] to leave a thymine base, so methylated cytosines are particularly prone to ]s.<ref>{{cite book | vauthors = Walsh CP, Xu GL | title = DNA Methylation: Basic Mechanisms | chapter = Cytosine methylation and DNA repair | volume = 301 | pages = 283–315 | year = 2006 | pmid = 16570853 | doi = 10.1007/3-540-31390-7_11 | isbn = 3-540-29114-8 | series = Current Topics in Microbiology and Immunology }}</ref> Other base modifications include adenine methylation in bacteria, the presence of ] in the ],<ref>{{cite journal | vauthors = Kriaucionis S, Heintz N | title = The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain | journal = Science | volume = 324 | issue = 5929 | pages = 929–30 | date = May 2009 | pmid = 19372393 | pmc = 3263819 | doi = 10.1126/science.1169786 | bibcode = 2009Sci...324..929K }}</ref> and the ] of uracil to produce the "J-base" in ].<ref>{{cite journal | vauthors = Ratel D, Ravanat JL, Berger F, Wion D | title = N6-methyladenine: the other methylated base of DNA | journal = BioEssays | volume = 28 | issue = 3 | pages = 309–15 | date = March 2006 | pmid = 16479578 | pmc = 2754416 | doi = 10.1002/bies.20342 }}</ref><ref>{{cite journal | vauthors = Gommers-Ampt JH, Van Leeuwen F, de Beer AL, Vliegenthart JF, Dizdaroglu M, Kowalak JA, Crain PF, Borst P | s2cid = 24801094 | title = beta-D-glucosyl-hydroxymethyluracil: a novel modified base present in the DNA of the parasitic protozoan T. brucei | journal = Cell | volume = 75 | issue = 6 | pages = 1129–36 | date = December 1993 | pmid = 8261512 | doi = 10.1016/0092-8674(93)90322-H | hdl = 1874/5219 | hdl-access = free }}</ref>


=== Damage ===
A distinct group of DNA-binding proteins are the single-stranded DNA-binding proteins. that specifically bind single-stranded DNA. In humans, replication protein A is the best-characterised member of this family and is essential for most processes where the double helix is separated, including DNA replication, recombination and DNA repair.<ref>{{cite journal | author = Iftode C, Daniely Y, Borowiec J | title = Replication protein A (RPA): the eukaryotic SSB | journal = Crit Rev Biochem Mol Biol | volume = 34 | issue = 3 | pages = 141-80 | year = 1999 | id = PMID 10473346}}</ref> These binding proteins seem to stabilize single-stranded DNA and protect it from forming ]s or being degraded by ]s.
{{further|DNA damage (naturally occurring)|Mutation|DNA damage theory of aging}}
] ] between a ] form of pyrene]], the major ] in ], and DNA<ref>Created from {{Webarchive|url=https://web.archive.org/web/20080922150848/http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1JDG |date=22 September 2008 }}</ref>]]


DNA can be damaged by many sorts of ]s, which change the ]. Mutagens include ]s, ] and also high-energy ] such as ] light and ]s. The type of DNA damage produced depends on the type of mutagen. For example, UV light can damage DNA by producing ]s, which are cross-links between pyrimidine bases.<ref>{{cite journal | vauthors = Douki T, Reynaud-Angelin A, Cadet J, Sage E | title = Bipyrimidine photoproducts rather than oxidative lesions are the main type of DNA damage involved in the genotoxic effect of solar UVA radiation | journal = Biochemistry | volume = 42 | issue = 30 | pages = 9221–26 | date = August 2003 | pmid = 12885257 | doi = 10.1021/bi034593c }}</ref> On the other hand, oxidants such as ] or ] produce multiple forms of damage, including base modifications, particularly of guanosine, and double-strand breaks.<ref>{{cite journal | vauthors = Cadet J, Delatour T, Douki T, Gasparutto D, Pouget JP, Ravanat JL, Sauvaigo S | title = Hydroxyl radicals and DNA base damage | journal = Mutation Research | volume = 424 | issue = 1–2 | pages = 9–21 | date = March 1999 | pmid = 10064846 | doi = 10.1016/S0027-5107(99)00004-4 | bibcode = 1999MRFMM.424....9C }}</ref> A typical human cell contains about 150,000 bases that have suffered oxidative damage.<ref>{{cite journal | vauthors = Beckman KB, Ames BN | title = Oxidative decay of DNA | journal = The Journal of Biological Chemistry | volume = 272 | issue = 32 | pages = 19633–36 | date = August 1997 | pmid = 9289489 | doi = 10.1074/jbc.272.32.19633 | doi-access = free }}</ref> Of these oxidative lesions, the most dangerous are double-strand breaks, as these are difficult to repair and can produce ]s, ], ] from the DNA sequence, and ]s.<ref>{{cite journal | vauthors = Valerie K, Povirk LF | title = Regulation and mechanisms of mammalian double-strand break repair | journal = Oncogene | volume = 22 | issue = 37 | pages = 5792–812 | date = September 2003 | pmid = 12947387 | doi = 10.1038/sj.onc.1206679 | doi-access = free }}</ref> These mutations can cause ]. Because of inherent limits in the DNA repair mechanisms, if humans lived long enough, they would all eventually develop cancer.<ref name=Weinberg>{{cite news | url = https://www.nytimes.com/2010/12/28/health/28cancer.html | title = Unearthing Prehistoric Tumors, and Debate | newspaper = ] | date = 28 December 2010 | vauthors = Johnson G | quote = If we lived long enough, sooner or later we all would get cancer. | url-status=live | archive-url = https://web.archive.org/web/20170624233156/http://www.nytimes.com/2010/12/28/health/28cancer.html | archive-date = 24 June 2017 | df = dmy-all }}</ref><ref>{{cite book |vauthors= Alberts B, Johnson A, Lewis J |title= Molecular biology of the cell |publisher= Garland Science |location= New York |year= 2002 |edition= 4th |chapter= The Preventable Causes of Cancer |isbn= 0-8153-4072-9 |chapter-url= https://www.ncbi.nlm.nih.gov/books/NBK26897/ |quote= A certain irreducible background incidence of cancer is to be expected regardless of circumstances: mutations can never be absolutely avoided, because they are an inescapable consequence of fundamental limitations on the accuracy of DNA replication, as discussed in Chapter 5. If a human could live long enough, it is inevitable that at least one of his or her cells would eventually accumulate a set of mutations sufficient for cancer to develop. |display-authors= etal |url-status=live |archive-url= https://web.archive.org/web/20160102193148/http://www.ncbi.nlm.nih.gov/books/NBK26897/ |archive-date= 2 January 2016 |df= dmy-all }}</ref> DNA damages that are ], due to normal cellular processes that produce reactive oxygen species, the hydrolytic activities of cellular water, etc., also occur frequently. Although most of these damages are repaired, in any cell some DNA damage may remain despite the action of repair processes. These remaining DNA damages accumulate with age in mammalian postmitotic tissues. This accumulation appears to be an important underlying cause of aging.<ref>{{cite book | veditors = Kimura H, Suzuki A | title = New Research on DNA Damage | date = 2008 | publisher = Nova Science Publishers | location = New York | isbn = 978-1-60456-581-2 | vauthors = Bernstein H, Payne CM, Bernstein C, Garewal H, Dvorak K | chapter = Cancer and aging as consequences of un-repaired DNA damage | chapter-url = https://www.novapublishers.com/catalog/product_info.php?products_id=43247 | pages = 1–47 | url-status=live | archive-url = https://web.archive.org/web/20141025091740/https://www.novapublishers.com/catalog/product_info.php?products_id=43247 | archive-date = 25 October 2014 | df = dmy-all }}</ref><ref>{{cite journal | vauthors = Hoeijmakers JH | title = DNA damage, aging, and cancer | journal = The New England Journal of Medicine | volume = 361 | issue = 15 | pages = 1475–85 | date = October 2009 | pmid = 19812404 | doi = 10.1056/NEJMra0804615 }}</ref><ref>{{cite journal | vauthors = Freitas AA, de Magalhães JP | title = A review and appraisal of the DNA damage theory of ageing | journal = Mutation Research | volume = 728 | issue = 1–2 | pages = 12–22 | year = 2011 | pmid = 21600302 | doi = 10.1016/j.mrrev.2011.05.001 | bibcode = 2011MRRMR.728...12F }}</ref>
] transcription factor bound to its DNA target.<ref>Created from </ref>]]
In contrast, other proteins have evolved to specifically bind particular DNA sequences. The most intensively studied of these are the various classes of ]s. These proteins control gene transcription. Each one of these proteins bind to one particular set of DNA sequences and thereby activates or inhibits the transcription of genes with these sequences close to their ]s. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins, this locates the polymerase at the promoter and allows it to begin transcription.<ref>{{cite journal | author = Myers L, Kornberg R | title = Mediator of transcriptional regulation | journal = Annu Rev Biochem | volume = 69 | issue = | pages = 729-49 | year = | id = PMID 10966474}}</ref> Alternatively, transcription factors can bind enzymes that modify the histones at the promoter, this will change the accessibility of the DNA template to the polymerase.<ref>{{cite journal | author = Spiegelman B, Heinrich R | title = Biological control through regulated transcriptional coactivators | journal = Cell | volume = 119 | issue = 2 | pages = 157-67 | year = 2004 | id = PMID 15479634}}</ref>


Many mutagens fit into the space between two adjacent base pairs, this is called '']''. Most intercalators are ] and planar molecules; examples include ], ]s, ], and ]. For an intercalator to fit between base pairs, the bases must separate, distorting the DNA strands by unwinding of the double helix. This inhibits both transcription and DNA replication, causing toxicity and mutations.<ref>{{cite journal | vauthors = Ferguson LR, Denny WA | title = The genetic toxicology of acridines | journal = Mutation Research | volume = 258 | issue = 2 | pages = 123–60 | date = September 1991 | pmid = 1881402 | doi = 10.1016/0165-1110(91)90006-H }}</ref> As a result, DNA intercalators may be ]s, and in the case of thalidomide, a ].<ref>{{cite journal | vauthors = Stephens TD, Bunde CJ, Fillmore BJ | title = Mechanism of action in thalidomide teratogenesis | journal = Biochemical Pharmacology | volume = 59 | issue = 12 | pages = 1489–99 | date = June 2000 | pmid = 10799645 | doi = 10.1016/S0006-2952(99)00388-3 }}</ref> Others such as pyrene diol epoxide]] and ] form DNA adducts that induce errors in replication.<ref>{{cite journal | vauthors = Jeffrey AM | title = DNA modification by chemical carcinogens | journal = Pharmacology & Therapeutics | volume = 28 | issue = 2 | pages = 237–72 | year = 1985 | pmid = 3936066 | doi = 10.1016/0163-7258(85)90013-0 }}</ref> Nevertheless, due to their ability to inhibit DNA transcription and replication, other similar toxins are also used in ] to inhibit rapidly growing ] cells.<ref>{{cite journal | vauthors = Braña MF, Cacho M, Gradillas A, de Pascual-Teresa B, Ramos A | title = Intercalators as anticancer drugs | journal = Current Pharmaceutical Design | volume = 7 | issue = 17 | pages = 1745–80 | date = November 2001 | pmid = 11562309 | doi = 10.2174/1381612013397113 }}</ref>
As these DNA targets can occur throughout an organism's genome, changes in the activity of one type of transcription factor can affect thousands of genes.<ref>{{cite journal | author = Li Z, Van Calcar S, Qu C, Cavenee W, Zhang M, Ren B | title = A global transcriptional regulatory role for c-Myc in Burkitt's lymphoma cells | url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=12808131 | journal = Proc Natl Acad Sci U S A | volume = 100 | issue = 14 | pages = 8164-9 | year = 2003 | id = PMID 12808131}}</ref> Consequently, these proteins are often the targets of the ] processes that mediate responses to environmental changes or cellular differentiation and development. The specificity of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of the DNA bases, allowing them to "read" the DNA sequence. Most of these base interactions are made in the major groove, where the bases are most accessible.<ref>{{cite journal | author = Pabo C, Sauer R | title = Protein-DNA recognition | journal = Annu Rev Biochem | volume = 53 | issue = | pages = 293-321 | year = | id = PMID 6236744}}</ref>


== Biological functions ==
] ] (green) in a complex with its substrate DNA.<ref>Created from </ref>]]
] within the chromosomes]]
DNA usually occurs as linear ]s in ]s, and ] in ]s. The set of chromosomes in a cell makes up its ]; the ] has approximately 3 billion base pairs of DNA arranged into 46 chromosomes.<ref name="Venter_2001" /> The information carried by DNA is held in the ] of pieces of DNA called ]s. ] of genetic information in genes is achieved via complementary base pairing. For example, in transcription, when a cell uses the information in a gene, the DNA sequence is copied into a complementary RNA sequence through the attraction between the DNA and the correct RNA nucleotides. Usually, this RNA copy is then used to make a matching ] in a process called ], which depends on the same interaction between RNA nucleotides. In an alternative fashion, a cell may copy its genetic information in a process called ]. The details of these functions are covered in other articles; here the focus is on the interactions between DNA and other molecules that mediate the function of the genome.


=== Genes and genomes ===
===DNA-modifying enzymes===
{{further|Cell nucleus|Chromatin|Chromosome|Gene|Noncoding DNA}}
====Nucleases and ligases====
Genomic DNA is tightly and orderly packed in the process called ], to fit the small available volumes of the cell. In eukaryotes, DNA is located in the ], with small amounts in ] and ]s. In prokaryotes, the DNA is held within an irregularly shaped body in the cytoplasm called the ].<ref>{{cite journal | vauthors = Thanbichler M, Wang SC, Shapiro L | title = The bacterial nucleoid: a highly organized and dynamic structure | journal = Journal of Cellular Biochemistry | volume = 96 | issue = 3 | pages = 506–21 | date = October 2005 | pmid = 15988757 | doi = 10.1002/jcb.20519 | doi-access = free }}</ref> The genetic information in a genome is held within genes, and the complete set of this information in an organism is called its ]. A gene is a unit of ] and is a region of DNA that influences a particular characteristic in an organism. Genes contain an ] that can be transcribed, and ]s such as ] and ], which control transcription of the open reading frame.
Nucleases are ]s that cut DNA strands by catalyzing the ] of the ]s. Nucleases that hydrolyse nucleotides from the ends of DNA strands are called ]s, while ]s cut within strands. The most frequently-used nucleases in ] are the ], which cut DNA at specific sequences. For instance, the EcoRV enzyme shown to the left recognizes the 6-base sequence 5'-GAT|ATC-3' and makes a cut at the vertical line. In nature, these enzymes protect ] against ] infection by digesting the phage DNA when it enters the bacterial cell, acting as part of the ].<ref>{{cite journal | author = Bickle T, Krüger D | title = Biology of DNA restriction | url=http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=372918&blobtype=pdf | journal = Microbiol Rev | volume = 57 | issue = 2 | pages = 434-50 | year = 1993 | id = PMID 8336674}}</ref> In technology, these sequence-specific nucleases are used in ] and ].


In many ], only a small fraction of the total sequence of the ] encodes protein. For example, only about 1.5% of the human genome consists of protein-coding ]s, with over 50% of human DNA consisting of non-coding ].<ref>{{cite journal | vauthors = Wolfsberg TG, McEntyre J, Schuler GD | title = Guide to the draft human genome | journal = Nature | volume = 409 | issue = 6822 | pages = 824–26 | date = February 2001 | pmid = 11236998 | doi = 10.1038/35057000 | bibcode = 2001Natur.409..824W | url = https://zenodo.org/record/1233093 | doi-access = free }}</ref> The reasons for the presence of so much ] in eukaryotic genomes and the extraordinary differences in ], or '']'', among species, represent a long-standing puzzle known as the "]".<ref>{{cite journal | vauthors = Gregory TR | title = The C-value enigma in plants and animals: a review of parallels and an appeal for partnership | journal = Annals of Botany | volume = 95 | issue = 1 | pages = 133–46 | date = January 2005 | pmid = 15596463 | doi = 10.1093/aob/mci009 | pmc = 4246714 }}</ref> However, some DNA sequences that do not code protein may still encode functional ] molecules, which are involved in the ].<ref name="Birney_2007" />
Enzymes called ]s can rejoin cut or broken DNA strands, using the energy from either ] or ].<ref name=Doherty>{{cite journal | author = Doherty A, Suh S | title = Structural and mechanistic conservation in DNA ligases. | url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=11058099 | journal = Nucleic Acids Res | volume = 28 | issue = 21 | pages = 4051-8 | year = 2000 | id = PMID 11058099}}</ref> Ligases are particularly important in ] DNA replication, as they join together the short segments of DNA produced at the ] into a complete copy of the DNA template. They are also used in ] and ].<ref name=Doherty/>
] (blue) producing an ] (green) from a DNA template (orange)<ref>{{Cite web| vauthors = Yin YW, Steitz TA |title=RCSB PDB – 1MSW: Structural basis for the transition from initiation to elongation transcription in T7 RNA polymerase|url=https://www.rcsb.org/structure/1MSW|access-date=2023-03-27|website=www.rcsb.org|language=en-US}}</ref>]]


Some noncoding DNA sequences play structural roles in chromosomes. ]s and ]s typically contain few genes but are important for the function and stability of chromosomes.<ref name=Nugent /><ref>{{cite journal | vauthors = Pidoux AL, Allshire RC | title = The role of heterochromatin in centromere function | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 360 | issue = 1455 | pages = 569–79 | date = March 2005 | pmid = 15905142 | pmc = 1569473 | doi = 10.1098/rstb.2004.1611 }}</ref> An abundant form of noncoding DNA in humans are ]s, which are copies of genes that have been disabled by mutation.<ref>{{cite journal | vauthors = Harrison PM, Hegyi H, Balasubramanian S, Luscombe NM, Bertone P, Echols N, Johnson T, Gerstein M | title = Molecular fossils in the human genome: identification and analysis of the pseudogenes in chromosomes 21 and 22 | journal = Genome Research | volume = 12 | issue = 2 | pages = 272–80 | date = February 2002 | pmid = 11827946 | pmc = 155275 | doi = 10.1101/gr.207102 }}</ref> These sequences are usually just molecular ]s, although they can occasionally serve as raw ] for the creation of new genes through the process of ] and ].<ref>{{cite journal | vauthors = Harrison PM, Gerstein M | title = Studying genomes through the aeons: protein families, pseudogenes and proteome evolution | journal = Journal of Molecular Biology | volume = 318 | issue = 5 | pages = 1155–74 | date = May 2002 | pmid = 12083509 | doi = 10.1016/S0022-2836(02)00109-2 }}</ref>
====Topoisomerases and helicases====
]s are enzymes with both nuclease and ligase activity. These proteins change the amount of ] in DNA. Some of these enzyme work by cutting the DNA helix and allowing one section to rotate, thereby reducing its level of supercoiling, the enzyme then seals the DNA break.<ref name=Champoux/> Other types of these enzymes are capable of cutting one DNA helix and then passing a second strand of DNA through this break, before rejoining the helix.<ref>{{cite journal | author = Schoeffler A, Berger J | title = Recent advances in understanding structure-function relationships in the type II topoisomerase mechanism | journal = Biochem Soc Trans | volume = 33 | issue = Pt 6 | pages = 1465-70 | year = 2005 | id = PMID 16246147}}</ref> Topoisomerases are required for many processes involving DNA, such as DNA replication and transcription.<ref name=Wang/>


=== Transcription and translation ===
Helicases are proteins that are a type of ]. They use the chemical energy in ] to break the hdrogen bonds between bases and unwind a DNA double helix into single strands.<ref>{{cite journal | author = Tuteja N, Tuteja R | title = Unraveling DNA helicases. Motif, structure, mechanism and function | url=http://www.blackwell-synergy.com/links/doi/10.1111%2Fj.1432-1033.2004.04094.x | journal = Eur J Biochem | volume = 271 | issue = 10 | pages = 1849-63 | year = 2004 | id = PMID 15128295}}</ref> These enzymes are essential for most processes where enzymes need to access the DNA bases.
{{further|Genetic code|Transcription (genetics)|Protein biosynthesis}}
A gene is a sequence of DNA that contains genetic information and can influence the ] of an organism. Within a gene, the sequence of bases along a DNA strand defines a ] sequence, which then defines one or more protein sequences. The relationship between the nucleotide sequences of genes and the ] sequences of proteins is determined by the rules of ], known collectively as the ]. The genetic code consists of three-letter 'words' called ''codons'' formed from a sequence of three nucleotides (e.g. ACT, CAG, TTT).


In transcription, the codons of a gene are copied into messenger RNA by ]. This RNA copy is then decoded by a ] that reads the RNA sequence by base-pairing the messenger RNA to ], which carries amino acids. Since there are 4 bases in 3-letter combinations, there are 64 possible codons (4<sup>3</sup>&nbsp;combinations). These encode the twenty ], giving most amino acids more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region; these are the TAG, TAA, and TGA codons, (UAG, UAA, and UGA on the mRNA).
====Polymerases====
Polymerases are enzymes that synthesise polynucleotide chains from ]s. They function by adding nucleotides onto the 3ˈ ] of the previous nucleotide in the DNA strand. As a consequence, all polymerases work in a 5' to 3' direction.<ref name=Joyce/> In the ] of these enzymes, the nucleoside triphosphate substrate base-pairs to a single-stranded polynucleotide template: this allows polymerases to accurately synthesise the complementary strand of this template. Polymerases are classified depending of the type of template they use.


=== Replication ===
In ] a DNA-dependent ] make a DNA copy of a DNA sequence. Accuracy is vital in this process, so many of these polymerases have a ] activity. Here, the polymerase recognizes the occasional mistakes in the synthesis reaction by the lack of base pairing between the mismatched nucleotides. If a mismatch is detected, a 3' to 5' ] activity is activated and the incorrect base removed.<ref>{{cite journal | author = Hubscher U, Maga G, Spadari S | title = Eukaryotic DNA polymerases | journal = Annu Rev Biochem | volume = 71 | issue = | pages = 133-63 | year = | id = PMID 12045093}}</ref> In most organisms DNA polymerases function in a large complex called the ] that contains multiple accessory subunits, such as the ] or ]s.<ref>{{cite journal | author = Johnson A, O'Donnell M | title = Cellular DNA replicases: components and dynamics at the replication fork | journal = Annu Rev Biochem | volume = 74 | issue = | pages = 283-315 | year = | id = PMID 15952889}}</ref>
{{further|DNA replication}}
] and ]. Next, one ] produces the ] copy. Another DNA polymerase binds to the ]. This enzyme makes discontinuous segments (called ]s) before ] joins them together.]]
] is essential for an organism to grow, but, when a cell divides, it must replicate the DNA in its genome so that the two daughter cells have the same genetic information as their parent. The double-stranded structure of DNA provides a simple mechanism for ]. Here, the two strands are separated and then each strand's ] sequence is recreated by an ] called ]. This enzyme makes the complementary strand by finding the correct base through complementary base pairing and bonding it onto the original strand. As DNA polymerases can only extend a DNA strand in a 5′ to 3′ direction, different mechanisms are used to copy the antiparallel strands of the double helix.<ref>{{cite journal | vauthors = Albà M | title = Replicative DNA polymerases | journal = Genome Biology | volume = 2 | issue = 1 | pages = REVIEWS3002 | year = 2001 | pmid = 11178285 | pmc = 150442 | doi = 10.1186/gb-2001-2-1-reviews3002 | doi-access = free }}</ref> In this way, the base on the old strand dictates which base appears on the new strand, and the cell ends up with a perfect copy of its DNA.


=== Extracellular nucleic acids ===
RNA-dependent DNA polymerases are a specialised class of polymerases that copy the sequence of a RNA strand into DNA. They include ], which is a ] enzyme involved in the infection of cells by ]es, and ], which is required for the replication of ]s.<ref>{{cite journal | author = Tarrago-Litvak L, Andréola M, Nevinsky G, Sarih-Cottin L, Litvak S | title = The reverse transcriptase of HIV-1: from enzymology to therapeutic intervention | url=http://www.fasebj.org/cgi/reprint/8/8/497 | journal = FASEB J | volume = 8 | issue = 8 | pages = 497-503 | year = 1994 | id = PMID 7514143}}</ref><ref name=Greider/> Telomerase is an unusual polymerase because it contains its own RNA template as part of its structure.<ref name=Nugent/>
Naked extracellular DNA (eDNA), most of it released by cell death, is nearly ubiquitous in the environment. Its concentration in soil may be as high as 2 μg/L, and its concentration in natural aquatic environments may be as high at 88 μg/L.<ref name=Tani_2010>{{cite book | vauthors = Tani K, Nasu M | veditors = Kikuchi Y, Rykova EY | title = Extracellular Nucleic Acids |url=https://archive.org/details/extracellularnuc00kiku |url-access=limited |publisher=Springer |date=2010 |pages=–38 |chapter=Roles of Extracellular DNA in Bacterial Ecosystems |isbn=978-3-642-12616-1}}</ref> Various possible functions have been proposed for eDNA: it may be involved in ];<ref name="Vlassov_2007">{{cite journal | vauthors = Vlassov VV, Laktionov PP, Rykova EY | title = Extracellular nucleic acids | journal = BioEssays | volume = 29 | issue = 7 | pages = 654–67 | date = July 2007 | pmid = 17563084 | doi = 10.1002/bies.20604 | s2cid = 32463239 }}</ref> it may provide nutrients;<ref name="pmid11591672">{{cite journal | vauthors = Finkel SE, Kolter R | title = DNA as a nutrient: novel role for bacterial competence gene homologs | journal = Journal of Bacteriology | volume = 183 | issue = 21 | pages = 6288–93 | date = November 2001 | pmid = 11591672 | pmc = 100116 | doi = 10.1128/JB.183.21.6288-6293.2001 }}</ref> and it may act as a buffer to recruit or titrate ions or antibiotics.<ref name=Mulcahy_2008>{{cite journal | vauthors = Mulcahy H, Charron-Mazenod L, Lewenza S | title = Extracellular DNA chelates cations and induces antibiotic resistance in Pseudomonas aeruginosa biofilms | journal = PLOS Pathogens | volume = 4 | issue = 11 | pages = e1000213 | date = November 2008 | pmid = 19023416 | pmc = 2581603 | doi = 10.1371/journal.ppat.1000213 | doi-access = free }}</ref> Extracellular DNA acts as a functional extracellular matrix component in the ]s of several bacterial species. It may act as a recognition factor to regulate the attachment and dispersal of specific cell types in the biofilm;<ref name=Berne_2010>{{cite journal | vauthors = Berne C, Kysela DT, Brun YV | title = A bacterial extracellular DNA inhibits settling of motile progeny cells within a biofilm | journal = Molecular Microbiology | volume = 77 | issue = 4 | pages = 815–29 | date = August 2010 | pmid = 20598083 | pmc = 2962764 | doi = 10.1111/j.1365-2958.2010.07267.x }}</ref> it may contribute to biofilm formation;<ref name=Whitchurch_2002>{{cite journal | vauthors = Whitchurch CB, Tolker-Nielsen T, Ragas PC, Mattick JS | title = Extracellular DNA required for bacterial biofilm formation | journal = Science | volume = 295 | issue = 5559 | pages = 1487 | date = February 2002 | pmid = 11859186 | doi = 10.1126/science.295.5559.1487 }}</ref> and it may contribute to the biofilm's physical strength and resistance to biological stress.<ref name=Hu_2012>{{cite journal | vauthors = Hu W, Li L, Sharma S, Wang J, McHardy I, Lux R, Yang Z, He X, Gimzewski JK, Li Y, Shi W | title = DNA builds and strengthens the extracellular matrix in Myxococcus xanthus biofilms by interacting with exopolysaccharides | journal = PLOS ONE | volume = 7 | issue = 12 | pages = e51905 | year = 2012 | pmid = 23300576 | pmc = 3530553 | doi = 10.1371/journal.pone.0051905 | bibcode = 2012PLoSO...751905H | doi-access = free }}</ref>


] is found in the blood of the mother, and can be sequenced to determine a great deal of information about the developing fetus.<ref name="Hui_2013">{{cite journal | vauthors = Hui L, Bianchi DW | title = Recent advances in the prenatal interrogation of the human fetal genome | journal = Trends in Genetics | volume = 29 | issue = 2 | pages = 84–91 | date = February 2013 | pmid = 23158400 | pmc = 4378900 | doi = 10.1016/j.tig.2012.10.013 }}</ref>
Transcription is carried out by a DNA-dependent ] that copies the sequence of a DNA strand into RNA. To begin transcribing a gene, the RNA polymerase binds to a sequence of DNA called a ] and separates the DNA strands. It then copies the gene sequence into a ] transcript until it reaches a region of DNA called the ], where it halts and detaches from the DNA. As with human DNA-dependent DNA polymerases, RNA polymerase II, the enzyme that transcribes most of the genes in the ], operates as part of a large protein complex with multiple regulatory and accessory subunits.<ref>{{cite journal | author = Martinez E | title = Multi-protein complexes in eukaryotic gene transcription | journal = Plant Mol Biol | volume = 50 | issue = 6 | pages = 925-47 | year = 2002 | id = PMID 12516863}}</ref>


Under the name of ] eDNA has seen increased use in the natural sciences as a survey tool for ], monitoring the movements and presence of species in water, air, or on land, and assessing an area's biodiversity.<ref>{{cite journal | vauthors = Foote AD, Thomsen PF, Sveegaard S, Wahlberg M, Kielgast J, Kyhn LA, Salling AB, Galatius A, Orlando L, Gilbert MT | display-authors = 6 | title = Investigating the potential use of environmental DNA (eDNA) for genetic monitoring of marine mammals | journal = PLOS ONE | volume = 7 | issue = 8 | pages = e41781 | year = 2012 | pmid = 22952587 | pmc = 3430683 | doi = 10.1371/journal.pone.0041781 | bibcode = 2012PLoSO...741781F | doi-access = free }}</ref><ref>{{Cite web | url=https://www.the-scientist.com/news-opinion/researchers-detect-land-animals-using-dna-in-nearby-water-bodies-67481 | title=Researchers Detect Land Animals Using DNA in Nearby Water Bodies}}</ref>
==Genetic recombination==

<div class="thumb tright" style="background-color: #f9f9f9; border: 1px solid #CCCCCC; margin:0.5em;">
=== Neutrophil extracellular traps ===
{|border="0" width=250px border="0" cellpadding="0" cellspacing="0" style="font-size: 85%; border: 1px solid #CCCCCC; margin: 0.3em;"
{{Main|Neutrophil extracellular traps}}
|]
Neutrophil extracellular traps (NETs) are networks of extracellular fibers, primarily composed of DNA, which allow ], a type of white blood cell, to kill extracellular pathogens while minimizing damage to the host cells.

== Interactions with proteins ==
All the functions of DNA depend on interactions with proteins. These ] can be non-specific, or the protein can bind specifically to a single DNA sequence. Enzymes can also bind to DNA and of these, the polymerases that copy the DNA base sequence in transcription and DNA replication are particularly important.

=== DNA-binding proteins ===
{{further|DNA-binding protein}}
]s (in blue). These proteins' basic amino acids bind to the acidic phosphate groups on DNA.]]

Structural proteins that bind DNA are well-understood examples of non-specific DNA-protein interactions. Within chromosomes, DNA is held in complexes with structural proteins. These proteins organize the DNA into a compact structure called ]. In eukaryotes, this structure involves DNA binding to a complex of small basic proteins called ]s, while in prokaryotes multiple types of proteins are involved.<ref>{{cite journal | vauthors = Sandman K, Pereira SL, Reeve JN | s2cid = 21101836 | title = Diversity of prokaryotic chromosomal proteins and the origin of the nucleosome | journal = Cellular and Molecular Life Sciences | volume = 54 | issue = 12 | pages = 1350–64 | date = December 1998 | pmid = 9893710 | doi = 10.1007/s000180050259 | pmc = 11147202 }}</ref><ref>{{cite journal | vauthors = Dame RT | title = The role of nucleoid-associated proteins in the organization and compaction of bacterial chromatin | journal = Molecular Microbiology | volume = 56 | issue = 4 | pages = 858–70 | date = May 2005 | pmid = 15853876 | doi = 10.1111/j.1365-2958.2005.04598.x | s2cid = 26965112 | doi-access = free }}</ref> The histones form a disk-shaped complex called a ], which contains two complete turns of double-stranded DNA wrapped around its surface. These non-specific interactions are formed through basic residues in the histones, making ]s to the acidic sugar-phosphate backbone of the DNA, and are thus largely independent of the base sequence.<ref>{{cite journal | vauthors = Luger K, Mäder AW, Richmond RK, Sargent DF, Richmond TJ | title = Crystal structure of the nucleosome core particle at 2.8 A resolution | journal = Nature | volume = 389 | issue = 6648 | pages = 251–60 | date = September 1997 | pmid = 9305837 | doi = 10.1038/38444 | bibcode = 1997Natur.389..251L | s2cid = 4328827 }}</ref> Chemical modifications of these basic amino acid residues include ], ], and ].<ref>{{cite journal | vauthors = Jenuwein T, Allis CD | title = Translating the histone code | journal = Science | volume = 293 | issue = 5532 | pages = 1074–80 | date = August 2001 | pmid = 11498575 | doi = 10.1126/science.1063127 | s2cid = 1883924 | url = http://www.gs.washington.edu/academics/courses/braun/55104/readings/jenuwein.pdf | url-status=live | archive-url = https://web.archive.org/web/20170808142426/http://www.gs.washington.edu/academics/courses/braun/55104/readings/jenuwein.pdf | archive-date = 8 August 2017 | df = dmy-all }}</ref> These chemical changes alter the strength of the interaction between the DNA and the histones, making the DNA more or less accessible to ]s and changing the rate of transcription.<ref>{{cite book | vauthors = Ito T | title = Protein Complexes that Modify Chromatin | chapter = Nucleosome Assembly and Remodeling | series = Current Topics in Microbiology and Immunology | volume = 274 | pages = 1–22 | year = 2003 | pmid = 12596902 | doi = 10.1007/978-3-642-55747-7_1 | isbn = 978-3-540-44208-0 }}</ref> Other non-specific DNA-binding proteins in chromatin include the high-mobility group proteins, which bind to bent or distorted DNA.<ref>{{cite journal | vauthors = Thomas JO | title = HMG1 and 2: architectural DNA-binding proteins | journal = Biochemical Society Transactions | volume = 29 | issue = Pt 4 | pages = 395–401 | date = August 2001 | pmid = 11497996 | doi = 10.1042/BST0290395 }}</ref> These proteins are important in bending arrays of nucleosomes and arranging them into the larger structures that make up chromosomes.<ref>{{cite journal | vauthors = Grosschedl R, Giese K, Pagel J | title = HMG domain proteins: architectural elements in the assembly of nucleoprotein structures | journal = Trends in Genetics | volume = 10 | issue = 3 | pages = 94–100 | date = March 1994 | pmid = 8178371 | doi = 10.1016/0168-9525(94)90232-1 }}</ref>

A distinct group of DNA-binding proteins is the DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication ] is the best-understood member of this family and is used in processes where the double helix is separated, including DNA replication, recombination, and DNA repair.<ref>{{cite journal | vauthors = Iftode C, Daniely Y, Borowiec JA | title = Replication protein A (RPA): the eukaryotic SSB | journal = Critical Reviews in Biochemistry and Molecular Biology | volume = 34 | issue = 3 | pages = 141–80 | year = 1999 | pmid = 10473346 | doi = 10.1080/10409239991209255 }}</ref> These binding proteins seem to stabilize single-stranded DNA and protect it from forming ]s or being degraded by ]s.

] transcription factor bound to its DNA target<ref>{{Cite web| vauthors = Beamer LJ, Pabo CO |title=RCSB PDB – 1LMB: Refined 1.8 Å crystal structure of the lambda repressor-operator complex |url=https://www.rcsb.org/structure/1LMB|access-date=2023-03-27|website=www.rcsb.org|language=en-US}}</ref>]]
In contrast, other proteins have evolved to bind to particular DNA sequences. The most intensively studied of these are the various ]s, which are proteins that regulate transcription. Each transcription factor binds to one particular set of DNA sequences and activates or inhibits the transcription of genes that have these sequences close to their promoters. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins; this locates the polymerase at the promoter and allows it to begin transcription.<ref>{{cite journal | vauthors = Myers LC, Kornberg RD | title = Mediator of transcriptional regulation | journal = Annual Review of Biochemistry | volume = 69 | pages = 729–49 | year = 2000 | pmid = 10966474 | doi = 10.1146/annurev.biochem.69.1.729 }}</ref> Alternatively, transcription factors can bind ]s that modify the histones at the promoter. This changes the accessibility of the DNA template to the polymerase.<ref>{{cite journal | vauthors = Spiegelman BM, Heinrich R | title = Biological control through regulated transcriptional coactivators | journal = Cell | volume = 119 | issue = 2 | pages = 157–67 | date = October 2004 | pmid = 15479634 | doi = 10.1016/j.cell.2004.09.037 | doi-access = free }}</ref>

As these DNA targets can occur throughout an organism's genome, changes in the activity of one type of transcription factor can affect thousands of genes.<ref>{{cite journal | vauthors = Li Z, Van Calcar S, Qu C, Cavenee WK, Zhang MQ, Ren B | title = A global transcriptional regulatory role for c-Myc in Burkitt's lymphoma cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 14 | pages = 8164–69 | date = July 2003 | pmid = 12808131 | pmc = 166200 | doi = 10.1073/pnas.1332764100 | bibcode = 2003PNAS..100.8164L | doi-access = free }}</ref> Consequently, these proteins are often the targets of the ] processes that control responses to environmental changes or ] and development. The specificity of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of the DNA bases, allowing them to "read" the DNA sequence. Most of these base-interactions are made in the major groove, where the bases are most accessible.<ref name="Pabo1984" />

=== DNA-modifying enzymes ===

==== Nucleases and ligases ====
] ] (green) in a complex with its substrate DNA<ref>{{Cite web| vauthors = Kostrewa D, Winkler FK |title=RCSB PDB – 1RVA: Mg2+ binding to the active site of EcoRV endonuclease: a crystallographic study of complexes with substrate and product DNA at 2 Å resolution |url=https://www.rcsb.org/structure/1RVA|access-date=2023-03-27|website=www.rcsb.org|language=en-US}}</ref>]]
]s are ]s that cut DNA strands by catalyzing the ] of the ]s. Nucleases that hydrolyse nucleotides from the ends of DNA strands are called ]s, while ]s cut within strands. The most frequently used nucleases in ] are the ], which cut DNA at specific sequences. For instance, the EcoRV enzyme shown to the left recognizes the 6-base sequence 5′-GATATC-3′ and makes a cut at the horizontal line. In nature, these enzymes protect ] against ] infection by digesting the phage DNA when it enters the bacterial cell, acting as part of the ].<ref>{{cite journal | vauthors = Bickle TA, Krüger DH | title = Biology of DNA restriction | journal = Microbiological Reviews | volume = 57 | issue = 2 | pages = 434–50 | date = June 1993 | pmid = 8336674 | pmc = 372918 | doi = 10.1128/MMBR.57.2.434-450.1993 }}</ref> In technology, these sequence-specific nucleases are used in ] and ].

Enzymes called ]s can rejoin cut or broken DNA strands.<ref name=Doherty>{{cite journal | vauthors = Doherty AJ, Suh SW | title = Structural and mechanistic conservation in DNA ligases | journal = Nucleic Acids Research | volume = 28 | issue = 21 | pages = 4051–58 | date = November 2000 | pmid = 11058099 | pmc = 113121 | doi = 10.1093/nar/28.21.4051 }}</ref> Ligases are particularly important in ] DNA replication, as they join the short segments of DNA produced at the ] into a complete copy of the DNA template. They are also used in ] and ].<ref name=Doherty />

==== Topoisomerases and helicases ====
]s are enzymes with both nuclease and ligase activity. These proteins change the amount of ] in DNA. Some of these enzymes work by cutting the DNA helix and allowing one section to rotate, thereby reducing its level of supercoiling; the enzyme then seals the DNA break.<ref name=Champoux /> Other types of these enzymes are capable of cutting one DNA helix and then passing a second strand of DNA through this break, before rejoining the helix.<ref>{{cite journal | vauthors = Schoeffler AJ, Berger JM | title = Recent advances in understanding structure-function relationships in the type II topoisomerase mechanism | journal = Biochemical Society Transactions | volume = 33 | issue = Pt 6 | pages = 1465–70 | date = December 2005 | pmid = 16246147 | doi = 10.1042/BST20051465 }}</ref> Topoisomerases are required for many processes involving DNA, such as DNA replication and transcription.<ref name=Wang />

]s are proteins that are a type of ]. They use the chemical energy in ]s, predominantly ] (ATP), to break hydrogen bonds between bases and unwind the DNA double helix into single strands.<ref>{{cite journal | vauthors = Tuteja N, Tuteja R | title = Unraveling DNA helicases. Motif, structure, mechanism and function | journal = European Journal of Biochemistry | volume = 271 | issue = 10 | pages = 1849–63 | date = May 2004 | pmid = 15128295 | doi = 10.1111/j.1432-1033.2004.04094.x | url = http://repository.ias.ac.in/52775/1/40-pub.pdf | doi-access = free }}</ref> These enzymes are essential for most processes where enzymes need to access the DNA bases.

==== Polymerases ====
]s are ]s that synthesize polynucleotide chains from ]s. The sequence of their products is created based on existing polynucleotide chains—which are called ''templates''. These enzymes function by repeatedly adding a nucleotide to the 3′ ] group at the end of the growing polynucleotide chain. As a consequence, all polymerases work in a 5′ to 3′ direction.<ref name=Joyce>{{cite journal | vauthors = Joyce CM, Steitz TA | title = Polymerase structures and function: variations on a theme? | journal = Journal of Bacteriology | volume = 177 | issue = 22 | pages = 6321–29 | date = November 1995 | pmid = 7592405 | pmc = 177480 | doi=10.1128/jb.177.22.6321-6329.1995}}</ref> In the ] of these enzymes, the incoming nucleoside triphosphate base-pairs to the template: this allows polymerases to accurately synthesize the complementary strand of their template. Polymerases are classified according to the type of template that they use.

In DNA replication, DNA-dependent ]s make copies of DNA polynucleotide chains. To preserve biological information, it is essential that the sequence of bases in each copy are precisely complementary to the sequence of bases in the template strand. Many DNA polymerases have a ] activity. Here, the polymerase recognizes the occasional mistakes in the synthesis reaction by the lack of base pairing between the mismatched nucleotides. If a mismatch is detected, a 3′ to 5′ ] activity is activated and the incorrect base removed.<ref>{{cite journal | vauthors = Hubscher U, Maga G, Spadari S | s2cid = 26171993 | title = Eukaryotic DNA polymerases | journal = Annual Review of Biochemistry | volume = 71 | pages = 133–63 | year = 2002 | pmid = 12045093 | doi = 10.1146/annurev.biochem.71.090501.150041 | url = http://pdfs.semanticscholar.org/e941/98efed7eb8fa606b87d9a44c118c235a62e9.pdf | archive-url = https://web.archive.org/web/20210126170051/http://pdfs.semanticscholar.org/e941/98efed7eb8fa606b87d9a44c118c235a62e9.pdf | url-status = dead | archive-date = 26 January 2021 }}</ref> In most organisms, DNA polymerases function in a large complex called the ] that contains multiple accessory subunits, such as the ] or ]s.<ref>{{cite journal | vauthors = Johnson A, O'Donnell M | title = Cellular DNA replicases: components and dynamics at the replication fork | journal = Annual Review of Biochemistry | volume = 74 | pages = 283–315 | year = 2005 | pmid = 15952889 | doi = 10.1146/annurev.biochem.73.011303.073859 }}</ref>

RNA-dependent DNA polymerases are a specialized class of polymerases that copy the sequence of an RNA strand into DNA. They include ], which is a ] enzyme involved in the infection of cells by ]es, and ], which is required for the replication of telomeres.<ref name=Greider /><ref name=Tarrago-Litvak1994>{{cite journal | vauthors = Tarrago-Litvak L, Andréola ML, Nevinsky GA, Sarih-Cottin L, Litvak S | title = The reverse transcriptase of HIV-1: from enzymology to therapeutic intervention | journal = FASEB Journal | volume = 8 | issue = 8 | pages = 497–503 | date = May 1994 | pmid = 7514143 | doi = 10.1096/fasebj.8.8.7514143 | doi-access = free | s2cid = 39614573 }}</ref> For example, HIV reverse transcriptase is an enzyme for AIDS virus replication.<ref name=Tarrago-Litvak1994 /> Telomerase is an unusual polymerase because it contains its own RNA template as part of its structure. It synthesizes ] at the ends of chromosomes. Telomeres prevent fusion of the ends of neighboring chromosomes and protect chromosome ends from damage.<ref name=Nugent />

Transcription is carried out by a DNA-dependent ] that copies the sequence of a DNA strand into RNA. To begin transcribing a gene, the RNA polymerase binds to a sequence of DNA called a promoter and separates the DNA strands. It then copies the gene sequence into a ] transcript until it reaches a region of DNA called the ], where it halts and detaches from the DNA. As with human DNA-dependent DNA polymerases, ], the enzyme that transcribes most of the genes in the human genome, operates as part of a large ] with multiple regulatory and accessory subunits.<ref>{{cite journal | vauthors = Martinez E | s2cid = 24946189 | title = Multi-protein complexes in eukaryotic gene transcription | journal = Plant Molecular Biology | volume = 50 | issue = 6 | pages = 925–47 | date = December 2002 | pmid = 12516863 | doi = 10.1023/A:1021258713850 }}</ref>

== Genetic recombination ==
{{further|Genetic recombination}}
<div class="thumb tright" style="background:#f9f9f9; border:1px solid #ccc; margin:0.5em;">
{| border="0" cellpadding="0" cellspacing="0" style="width:250px; font-size:85%; border:1px solid #ccc; margin:0.3em;"
|- |-
|] |]
|-
|]
|} |}
<div style="border: none; width:250px;"><div class="thumbcaption">Structure of the ] intermediate in ]. The four separate DNA strands are coloured red, blue, green and yellow.<ref>Created from </ref></div></div></div> <div style="border: none; width:250px;"><div class="thumbcaption">Structure of the ] intermediate in ]. The four separate DNA strands are coloured red, blue, green and yellow.<ref>{{Cite web| vauthors = Thorpe JH, Gale BC, Teixeira SC, Cardin CJ |title=RCSB PDB – 1M6G: Structural Characterisation of the Holliday Junction TCGGTACCGA|url=https://www.rcsb.org/structure/1M6G|access-date=2023-03-27|website=www.rcsb.org|language=en-US}}</ref></div></div></div>
]
{{further|]}}

]
A DNA helix usually does not interact with other segments of DNA, and in human cells, the different chromosomes even occupy separate areas in the nucleus called "]".<ref>{{cite journal | vauthors = Cremer T, Cremer C | title = Chromosome territories, nuclear architecture and gene regulation in mammalian cells | journal = Nature Reviews Genetics | volume = 2 | issue = 4 | pages = 292–301 | date = April 2001 | pmid = 11283701 | doi = 10.1038/35066075 | s2cid = 8547149 }}</ref> This physical separation of different chromosomes is important for the ability of DNA to function as a stable repository for information, as one of the few times chromosomes interact is in ] which occurs during ], when ] occurs. Chromosomal crossover is when two DNA helices break, swap a section and then rejoin.

Recombination allows chromosomes to exchange genetic information and produces new combinations of genes, which increases the efficiency of ] and can be important in the rapid evolution of new proteins.<ref>{{cite journal | vauthors = Pál C, Papp B, Lercher MJ | title = An integrated view of protein evolution | journal = Nature Reviews Genetics | volume = 7 | issue = 5 | pages = 337–48 | date = May 2006 | pmid = 16619049 | doi = 10.1038/nrg1838 | s2cid = 23225873 }}</ref> Genetic recombination can also be involved in DNA repair, particularly in the cell's response to double-strand breaks.<ref>{{cite journal | vauthors = O'Driscoll M, Jeggo PA | title = The role of double-strand break repair – insights from human genetics | journal = Nature Reviews Genetics | volume = 7 | issue = 1 | pages = 45–54 | date = January 2006 | pmid = 16369571 | doi = 10.1038/nrg1746 | s2cid = 7779574 }}</ref>

The most common form of chromosomal crossover is ], where the two chromosomes involved share very similar sequences. ] can be damaging to cells, as it can produce ]s and genetic abnormalities. The recombination reaction is catalyzed by enzymes known as ]s, such as ].<ref>{{cite journal | vauthors = Vispé S, Defais M | title = Mammalian Rad51 protein: a RecA homologue with pleiotropic functions | journal = Biochimie | volume = 79 | issue = 9–10 | pages = 587–92 | date = October 1997 | pmid = 9466696 | doi = 10.1016/S0300-9084(97)82007-X }}</ref> The first step in recombination is a double-stranded break caused by either an ] or damage to the DNA.<ref>{{cite journal | vauthors = Neale MJ, Keeney S | title = Clarifying the mechanics of DNA strand exchange in meiotic recombination | journal = Nature | volume = 442 | issue = 7099 | pages = 153–58 | date = July 2006 | pmid = 16838012 | doi = 10.1038/nature04885 | bibcode = 2006Natur.442..153N | pmc = 5607947 }}</ref> A series of steps catalyzed in part by the recombinase then leads to joining of the two helices by at least one ], in which a segment of a single strand in each helix is annealed to the complementary strand in the other helix. The Holliday junction is a tetrahedral junction structure that can be moved along the pair of chromosomes, swapping one strand for another. The recombination reaction is then halted by cleavage of the junction and re-ligation of the released DNA.<ref>{{cite journal | vauthors = Dickman MJ, Ingleston SM, Sedelnikova SE, Rafferty JB, Lloyd RG, Grasby JA, Hornby DP | s2cid = 39505263 | title = The RuvABC resolvasome | journal = European Journal of Biochemistry | volume = 269 | issue = 22 | pages = 5492–501 | date = November 2002 | pmid = 12423347 | doi = 10.1046/j.1432-1033.2002.03250.x | doi-access = free }}</ref> Only strands of like polarity exchange DNA during recombination. There are two types of cleavage: east-west cleavage and north–south cleavage. The north–south cleavage nicks both strands of DNA, while the east–west cleavage has one strand of DNA intact. The formation of a Holliday junction during recombination makes it possible for genetic diversity, genes to exchange on chromosomes, and expression of wild-type viral genomes.

== Evolution ==
{{further|RNA world hypothesis}}
DNA contains the genetic information that allows all forms of life to function, grow and reproduce. However, it is unclear how long in the 4-billion-year ] DNA has performed this function, as it has been proposed that the earliest forms of life may have used RNA as their genetic material.<ref name="Joyce-2002">{{cite journal | vauthors = Joyce GF | title = The antiquity of RNA-based evolution | journal = Nature | volume = 418 | issue = 6894 | pages = 214–21 | date = July 2002 | pmid = 12110897 | doi = 10.1038/418214a | bibcode = 2002Natur.418..214J | s2cid = 4331004 }}</ref><ref>{{cite journal | vauthors = Orgel LE | title = Prebiotic chemistry and the origin of the RNA world | journal = Critical Reviews in Biochemistry and Molecular Biology | volume = 39 | issue = 2 | pages = 99–123 | year = 2004 | pmid = 15217990 | doi = 10.1080/10409230490460765 | citeseerx = 10.1.1.537.7679 | s2cid = 4939632 }}</ref> RNA may have acted as the central part of early ] as it can both transmit genetic information and carry out ] as part of ]s.<ref>{{cite journal | vauthors = Davenport RJ | s2cid = 85976762 | title = Ribozymes. Making copies in the RNA world | journal = Science | volume = 292 | issue = 5520 | pages = 1278a–1278 | date = May 2001 | pmid = 11360970 | doi = 10.1126/science.292.5520.1278a }}</ref> This ancient ] where nucleic acid would have been used for both catalysis and genetics may have influenced the ] of the current genetic code based on four nucleotide bases. This would occur, since the number of different bases in such an organism is a trade-off between a small number of bases increasing replication accuracy and a large number of bases increasing the catalytic efficiency of ribozymes.<ref>{{cite journal | vauthors = Szathmáry E | title = What is the optimum size for the genetic alphabet? | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 7 | pages = 2614–18 | date = April 1992 | pmid = 1372984 | pmc = 48712 | doi = 10.1073/pnas.89.7.2614 | bibcode = 1992PNAS...89.2614S | doi-access = free }}</ref> However, there is no direct evidence of ancient genetic systems, as recovery of DNA from most fossils is impossible because DNA survives in the environment for less than one million years, and slowly degrades into short fragments in solution.<ref>{{cite journal | vauthors = Lindahl T | title = Instability and decay of the primary structure of DNA | journal = Nature | volume = 362 | issue = 6422 | pages = 709–15 | date = April 1993 | pmid = 8469282 | doi = 10.1038/362709a0 | bibcode = 1993Natur.362..709L | s2cid = 4283694 }}</ref> Claims for older DNA have been made, most notably a report of the isolation of a viable bacterium from a salt crystal 250 million years old,<ref>{{cite journal | vauthors = Vreeland RH, Rosenzweig WD, Powers DW | title = Isolation of a 250 million-year-old halotolerant bacterium from a primary salt crystal | journal = Nature | volume = 407 | issue = 6806 | pages = 897–900 | date = October 2000 | pmid = 11057666 | doi = 10.1038/35038060 | bibcode = 2000Natur.407..897V | s2cid = 9879073 }}</ref> but these claims are controversial.<ref>{{cite journal | vauthors = Hebsgaard MB, Phillips MJ, Willerslev E | title = Geologically ancient DNA: fact or artefact? | journal = Trends in Microbiology | volume = 13 | issue = 5 | pages = 212–20 | date = May 2005 | pmid = 15866038 | doi = 10.1016/j.tim.2005.03.010 }}</ref><ref>{{cite journal | vauthors = Nickle DC, Learn GH, Rain MW, Mullins JI, Mittler JE | title = Curiously modern DNA for a "250 million-year-old" bacterium | journal = Journal of Molecular Evolution | volume = 54 | issue = 1 | pages = 134–37 | date = January 2002 | pmid = 11734907 | doi = 10.1007/s00239-001-0025-x | bibcode = 2002JMolE..54..134N | s2cid = 24740859 }}</ref>

Building blocks of DNA (], ], and related ]) may have been formed extraterrestrially in ].<ref name="Callahan">{{cite journal | vauthors = Callahan MP, Smith KE, Cleaves HJ, Ruzicka J, Stern JC, Glavin DP, House CH, Dworkin JP | title = Carbonaceous meteorites contain a wide range of extraterrestrial nucleobases | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 34 | pages = 13995–98 | date = August 2011 | pmid = 21836052 | pmc = 3161613 | doi = 10.1073/pnas.1106493108 | bibcode = 2011PNAS..10813995C | doi-access = free }}</ref><ref name="Steigerwald">{{cite web | vauthors = Steigerwald J |title=NASA Researchers: DNA Building Blocks Can Be Made in Space |url=http://www.nasa.gov/topics/solarsystem/features/dna-meteorites.html |publisher=] |date=8 August 2011 |access-date=10 August 2011 |url-status=live |archive-url=https://web.archive.org/web/20150623004556/http://www.nasa.gov/topics/solarsystem/features/dna-meteorites.html |archive-date=23 June 2015 }}</ref><ref name="DNA">{{cite web |author=ScienceDaily Staff |title=DNA Building Blocks Can Be Made in Space, NASA Evidence Suggests |url=https://www.sciencedaily.com/releases/2011/08/110808220659.htm |date=9 August 2011 |website=] |access-date=9 August 2011 |url-status=live |archive-url=https://web.archive.org/web/20110905105043/https://www.sciencedaily.com/releases/2011/08/110808220659.htm |archive-date=5 September 2011 }}</ref> Complex DNA and ] ]s of ], including ], ], and ], have also been formed in the laboratory under conditions mimicking those found in ], using starting chemicals, such as ], found in ]s. Pyrimidine, like ] (PAHs), the most carbon-rich chemical found in the ], may have been formed in ]s or in interstellar ] and gas clouds.<ref name="NASA-20150303">{{cite web | vauthors = Marlaire R |title=NASA Ames Reproduces the Building Blocks of Life in Laboratory |url=http://www.nasa.gov/content/nasa-ames-reproduces-the-building-blocks-of-life-in-laboratory |date=3 March 2015 |work=] |access-date=5 March 2015 |url-status=live |archive-url=https://web.archive.org/web/20150305083306/http://www.nasa.gov/content/nasa-ames-reproduces-the-building-blocks-of-life-in-laboratory/ |archive-date=5 March 2015 }}</ref>

] has been recovered from ancient organisms at a timescale where genome evolution can be directly observed, including from extinct organisms up to millions of years old, such as the ].<ref name="CNN-20210217">{{cite news | vauthors = Hunt K |title=World's oldest DNA sequenced from a mammoth that lived more than a million years ago |url=https://www.cnn.com/2021/02/17/world/mammoth-oldest-dna-million-years-ago-scn/index.html |date=17 February 2021 |work=] |access-date=17 February 2021 }}</ref><ref name="NAT-20210217">{{cite journal | vauthors = Callaway E | title = Million-year-old mammoth genomes shatter record for oldest ancient DNA – Permafrost-preserved teeth, up to 1.6 million years old, identify a new kind of mammoth in Siberia. |date=17 February 2021 |journal=] |volume=590 |issue=7847 |pages=537–538 |doi=10.1038/d41586-021-00436-x |issn=0028-0836 |pmid=33597786 | bibcode = 2021Natur.590..537C |doi-access=free }}</ref>

== Uses in technology ==

=== Genetic engineering ===
{{further|Molecular biology|Nucleic acid methods|Genetic engineering}}
Methods have been developed to purify DNA from organisms, such as ], and to manipulate it in the laboratory, such as ]s and the ]. Modern ] and ] make intensive use of these techniques in recombinant DNA technology. ] is a man-made DNA sequence that has been assembled from other DNA sequences. They can be ] into organisms in the form of ]s or in the appropriate format, by using a ].<ref>{{cite journal | vauthors = Goff SP, Berg P | s2cid = 41788896 | title = Construction of hybrid viruses containing SV40 and lambda phage DNA segments and their propagation in cultured monkey cells | journal = Cell | volume = 9 | issue = 4 PT 2 | pages = 695–705 | date = December 1976 | pmid = 189942 | doi = 10.1016/0092-8674(76)90133-1 }}</ref> The ] organisms produced can be used to produce products such as recombinant ]s, used in ],<ref>{{cite book | vauthors = Houdebine LM | title = Target Discovery and Validation Reviews and Protocols | chapter = Transgenic animal models in biomedical research | series = Methods in Molecular Biology | volume = 360 | pages = 163–202 | year = 2007 | pmid = 17172731 | doi = 10.1385/1-59745-165-7:163 | isbn = 978-1-59745-165-9 }}</ref> or be grown in ].<ref>{{cite journal | vauthors = Daniell H, Dhingra A | title = Multigene engineering: dawn of an exciting new era in biotechnology | journal = Current Opinion in Biotechnology | volume = 13 | issue = 2 | pages = 136–41 | date = April 2002 | pmid = 11950565 | pmc = 3481857 | doi = 10.1016/S0958-1669(02)00297-5 }}</ref><ref>{{cite journal | vauthors = Job D | title = Plant biotechnology in agriculture | journal = Biochimie | volume = 84 | issue = 11 | pages = 1105–10 | date = November 2002 | pmid = 12595138 | doi = 10.1016/S0300-9084(02)00013-5 }}</ref>

=== DNA profiling ===
{{further|DNA profiling}}

] can use DNA in ], ], ], ] or ] found at a ] to identify a matching DNA of an individual, such as a perpetrator.<ref>{{Cite news|url=https://theconversation.com/from-the-crime-scene-to-the-courtroom-the-journey-of-a-dna-sample-82250|title=From the crime scene to the courtroom: the journey of a DNA sample| vauthors = Curtis C, Hereward J |date=29 August 2017 |work=The Conversation |access-date=22 October 2017 |archive-url=https://web.archive.org/web/20171022033110/http://theconversation.com/from-the-crime-scene-to-the-courtroom-the-journey-of-a-dna-sample-82250 |archive-date=22 October 2017 |url-status=live }}</ref> This process is formally termed ], also called ''DNA fingerprinting''. In DNA profiling, the lengths of variable sections of repetitive DNA, such as ]s and ]s, are compared between people. This method is usually an extremely reliable technique for identifying a matching DNA.<ref>{{cite journal | vauthors = Collins A, Morton NE | title = Likelihood ratios for DNA identification | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 91 | issue = 13 | pages = 6007–11 | date = June 1994 | pmid = 8016106 | pmc = 44126 | doi = 10.1073/pnas.91.13.6007 | bibcode = 1994PNAS...91.6007C | doi-access = free }}</ref> However, identification can be complicated if the scene is contaminated with DNA from several people.<ref>{{cite journal | vauthors = Weir BS, Triggs CM, Starling L, Stowell LI, Walsh KA, Buckleton J | title = Interpreting DNA mixtures | journal = Journal of Forensic Sciences | volume = 42 | issue = 2 | pages = 213–22 | date = March 1997 | doi = 10.1520/JFS14100J | pmid = 9068179 | s2cid = 14511630 }}</ref> DNA profiling was developed in 1984 by British geneticist Sir ],<ref>{{cite journal | vauthors = Jeffreys AJ, Wilson V, Thein SL | title = Individual-specific 'fingerprints' of human DNA | journal = Nature | volume = 316 | issue = 6023 | pages = 76–79 | year = 1985 | pmid = 2989708 | doi = 10.1038/316076a0 | bibcode = 1985Natur.316...76J | s2cid = 4229883 | doi-access = free }}</ref> and first used in forensic science to convict Colin Pitchfork in the 1988 ] case.<ref>{{Cite web|date=2006-12-14|title=Colin Pitchfork|url=http://www.forensic.gov.uk/forensic_t/inside/news/list_casefiles.php?case=1|access-date=2023-03-27|archive-url=https://web.archive.org/web/20061214004903/http://www.forensic.gov.uk/forensic_t/inside/news/list_casefiles.php?case=1 |archive-date=14 December 2006 }}</ref>

The development of forensic science and the ability to now obtain genetic matching on minute samples of blood, skin, saliva, or hair has led to re-examining many cases. Evidence can now be uncovered that was scientifically impossible at the time of the original examination. Combined with the removal of the ] law in some places, this can allow cases to be reopened where prior trials have failed to produce sufficient evidence to convince a jury. People charged with serious crimes may be required to provide a sample of DNA for matching purposes. The most obvious defense to DNA matches obtained forensically is to claim that cross-contamination of evidence has occurred. This has resulted in meticulous strict handling procedures with new cases of serious crime.

DNA profiling is also used successfully to positively identify victims of mass casualty incidents,<ref>{{cite web|url=http://massfatality.dna.gov/Introduction/ |title=DNA Identification in Mass Fatality Incidents |date=September 2006 |publisher=National Institute of Justice |url-status=dead |archive-url=https://web.archive.org/web/20061112000837/http://massfatality.dna.gov/Introduction/ |archive-date=12 November 2006 }}</ref> bodies or body parts in serious accidents, and individual victims in mass war graves, via matching to family members.

DNA profiling is also used in ] to determine if someone is the biological parent or grandparent of a child with the probability of parentage is typically 99.99% when the alleged parent is biologically related to the child. Normal ] methods happen after birth, but there are new methods to test paternity while a mother is still pregnant.<ref>{{Cite news| vauthors = Pollack A |date=2012-06-19|title=Before Birth, Dad's ID|language=en-US|work=The New York Times|url=https://www.nytimes.com/2012/06/20/health/paternity-blood-tests-that-work-early-in-a-pregnancy.html|access-date=2023-03-27|issn=0362-4331|archive-url=https://web.archive.org/web/20170624231639/http://www.nytimes.com/2012/06/20/health/paternity-blood-tests-that-work-early-in-a-pregnancy.html|archive-date=2017-06-24|url-status=live}}</ref>

=== DNA enzymes or catalytic DNA ===
{{further|Deoxyribozyme}}
]s, also called DNAzymes or catalytic DNA, were first discovered in 1994.<ref name="Breaker 223–229">{{cite journal | vauthors = Breaker RR, Joyce GF | title = A DNA enzyme that cleaves RNA | journal = Chemistry & Biology | volume = 1 | issue = 4 | pages = 223–29 | date = December 1994 | pmid = 9383394 | doi = 10.1016/1074-5521(94)90014-0 }}</ref> They are mostly single stranded DNA sequences isolated from a large pool of random DNA sequences through a combinatorial approach called ] selection or ] (SELEX). DNAzymes catalyze variety of chemical reactions including RNA-DNA cleavage, RNA-DNA ligation, amino acids phosphorylation-dephosphorylation, carbon-carbon bond formation, etc. DNAzymes can enhance catalytic rate of chemical reactions up to 100,000,000,000-fold over the uncatalyzed reaction.<ref>{{cite journal | vauthors = Chandra M, Sachdeva A, Silverman SK | title = DNA-catalyzed sequence-specific hydrolysis of DNA | journal = Nature Chemical Biology | volume = 5 | issue = 10 | pages = 718–20 | date = October 2009 | pmid = 19684594 | pmc = 2746877 | doi = 10.1038/nchembio.201 }}</ref> The most extensively studied class of DNAzymes is RNA-cleaving types which have been used to detect different metal ions and designing therapeutic agents. Several metal-specific DNAzymes have been reported including the GR-5 DNAzyme (lead-specific),<ref name="Breaker 223–229" /> the CA1-3 DNAzymes (copper-specific),<ref>{{cite journal | vauthors = Carmi N, Shultz LA, Breaker RR | title = In vitro selection of self-cleaving DNAs | journal = Chemistry & Biology | volume = 3 | issue = 12 | pages = 1039–46 | date = December 1996 | pmid = 9000012 | doi = 10.1016/S1074-5521(96)90170-2 | doi-access = free }}</ref> the 39E DNAzyme (uranyl-specific) and the NaA43 DNAzyme (sodium-specific).<ref>{{cite journal | vauthors = Torabi SF, Wu P, McGhee CE, Chen L, Hwang K, Zheng N, Cheng J, Lu Y | title = In vitro selection of a sodium-specific DNAzyme and its application in intracellular sensing | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 19 | pages = 5903–08 | date = May 2015 | pmid = 25918425 | pmc = 4434688 | doi = 10.1073/pnas.1420361112 | bibcode = 2015PNAS..112.5903T | doi-access = free }}</ref> The NaA43 DNAzyme, which is reported to be more than 10,000-fold selective for sodium over other metal ions, was used to make a real-time sodium sensor in cells.

=== Bioinformatics ===
{{further|Bioinformatics}}
] involves the development of techniques to store, ], search and manipulate biological data, including DNA ] data. These have led to widely applied advances in ], especially ]s, ], and ].<ref>{{cite book | vauthors = Baldi P, Brunak S |author1-link=Pierre Baldi |title=Bioinformatics: The Machine Learning Approach |publisher= MIT Press |year=2001| isbn=978-0-262-02506-5 |oclc=45951728}}</ref> String searching or matching algorithms, which find an occurrence of a sequence of letters inside a larger sequence of letters, were developed to search for specific sequences of nucleotides.<ref>{{cite book | vauthors = Gusfield D | title = Algorithms on Strings, Trees, and Sequences: Computer Science and Computational Biology | publisher = ] | date = 15 January 1997 | isbn = 978-0-521-58519-4 }}</ref> The DNA sequence may be ] with other DNA sequences to identify ] and locate the specific ]s that make them distinct. These techniques, especially ], are used in studying ] relationships and protein function.<ref>{{cite journal | vauthors = Sjölander K | title = Phylogenomic inference of protein molecular function: advances and challenges | journal = Bioinformatics | volume = 20 | issue = 2 | pages = 170–79 | date = January 2004 | pmid = 14734307 | doi = 10.1093/bioinformatics/bth021 | citeseerx = 10.1.1.412.943 }}</ref> Data sets representing entire genomes' worth of DNA sequences, such as those produced by the ], are difficult to use without the annotations that identify the locations of genes and regulatory elements on each chromosome. Regions of DNA sequence that have the characteristic patterns associated with protein- or RNA-coding genes can be identified by ] algorithms, which allow researchers to predict the presence of particular ]s and their possible functions in an organism even before they have been isolated experimentally.<ref name="Mount">{{cite book | vauthors = Mount DM |title=Bioinformatics: Sequence and Genome Analysis |edition= 2nd |publisher= Cold Spring Harbor Laboratory Press |year= 2004 |isbn= 0-87969-712-1|oclc= 55106399|location=Cold Spring Harbor, NY}}</ref> Entire genomes may also be compared, which can shed light on the evolutionary history of particular organism and permit the examination of complex evolutionary events.

=== DNA nanotechnology ===
{{further|DNA nanotechnology}}
] at right. ] is the field that seeks to design nanoscale structures using the ] properties of DNA molecules.<ref>{{cite journal | vauthors = Strong M | title = Protein nanomachines | journal = PLOS Biology | volume = 2 | issue = 3 | pages = E73 | date = March 2004 | pmid = 15024422 | pmc = 368168 | doi = 10.1371/journal.pbio.0020073 | s2cid = 13222080 | doi-access = free }}</ref>]]
DNA nanotechnology uses the unique ] properties of DNA and other nucleic acids to create self-assembling branched DNA complexes with useful properties.<ref>{{cite journal | vauthors = Rothemund PW | s2cid = 4316391 | title = Folding DNA to create nanoscale shapes and patterns | journal = Nature | volume = 440 | issue = 7082 | pages = 297–302 | date = March 2006 | pmid = 16541064 | doi = 10.1038/nature04586 | bibcode = 2006Natur.440..297R | url = https://authors.library.caltech.edu/22244/3/nature04586-s2.pdf }}</ref> DNA is thus used as a structural material rather than as a carrier of biological information. This has led to the creation of two-dimensional periodic lattices (both tile-based and using the '']'' method) and three-dimensional structures in the shapes of ].<ref>{{cite journal | vauthors = Andersen ES, Dong M, Nielsen MM, Jahn K, Subramani R, Mamdouh W, Golas MM, Sander B, Stark H, Oliveira CL, Pedersen JS, Birkedal V, Besenbacher F, Gothelf KV, Kjems J | s2cid = 4430815 | title = Self-assembly of a nanoscale DNA box with a controllable lid | journal = Nature | volume = 459 | issue = 7243 | pages = 73–76 | date = May 2009 | pmid = 19424153 | doi = 10.1038/nature07971 | bibcode = 2009Natur.459...73A | hdl = 11858/00-001M-0000-0010-9362-B | hdl-access = free }}</ref> ] and ] have also been demonstrated,<ref>{{cite journal | vauthors = Ishitsuka Y, Ha T | title = DNA nanotechnology: a nanomachine goes live | journal = Nature Nanotechnology | volume = 4 | issue = 5 | pages = 281–82 | date = May 2009 | pmid = 19421208 | doi = 10.1038/nnano.2009.101 | bibcode = 2009NatNa...4..281I }}</ref> and these DNA structures have been used to template the arrangement of other molecules such as ] and ] proteins.<ref>{{cite journal | vauthors = Aldaye FA, Palmer AL, Sleiman HF | title = Assembling materials with DNA as the guide | journal = Science | volume = 321 | issue = 5897 | pages = 1795–99 | date = September 2008 | pmid = 18818351 | doi = 10.1126/science.1154533 | bibcode = 2008Sci...321.1795A | s2cid = 2755388 }}</ref> DNA and other nucleic acids are the basis of ], synthetic oligonucleotide ligands for specific target molecules used in a range of biotechnology and biomedical applications.<ref>{{cite journal | vauthors = Dunn MR, Jimenez RM, Chaput JC |title=Analysis of aptamer discovery and technology |journal=Nature Reviews Chemistry |date=2017 |volume=1 |issue=10 |doi=10.1038/s41570-017-0076 |url=https://www.nature.com/articles/s41570-017-0076 |access-date=30 June 2022}}</ref>

=== History and anthropology ===
{{further|Phylogenetics|Genetic genealogy}}
Because DNA collects mutations over time, which are then inherited, it contains historical information, and, by comparing DNA sequences, geneticists can infer the evolutionary history of organisms, their ].<ref>{{cite journal | vauthors = Wray GA | title = Dating branches on the tree of life using DNA | journal = Genome Biology | volume = 3 | issue = 1 | pages = REVIEWS0001 | year = 2002 | pmid = 11806830 | pmc = 150454 | doi = 10.1186/gb-2001-3-1-reviews0001 | doi-access = free }}</ref> This field of phylogenetics is a powerful tool in ]. If DNA sequences within a species are compared, ] can learn the history of particular populations. This can be used in studies ranging from ] to ].

=== Information storage ===
{{Main|DNA digital data storage}}

DNA as a ] for information has enormous potential since it has much higher ] compared to electronic devices. However, high costs, slow read and write times (]), and insufficient ] has prevented its practical use.<ref name="pmid29744271">{{cite journal | vauthors = Panda D, Molla KA, Baig MJ, Swain A, Behera D, Dash M | title = DNA as a digital information storage device: hope or hype? | journal = 3 Biotech | volume = 8 | issue = 5 | pages = 239 | date = May 2018 | pmid = 29744271 | doi = 10.1007/s13205-018-1246-7 | pmc=5935598}}</ref><ref name="pmid30073589">{{cite journal | vauthors = Akram F, Haq IU, Ali H, Laghari AT | s2cid = 51905843 | title = Trends to store digital data in DNA: an overview | journal = Molecular Biology Reports | volume = 45 | issue = 5 | pages = 1479–1490 | date = October 2018 | pmid = 30073589 | doi = 10.1007/s11033-018-4280-y }}</ref>

== History ==
{{anchor|History of DNA research}}
{{further|History of molecular biology}}
] (left) shakes hands with ] and ], co-originators of the double-helix model based on the X-ray diffraction data and insights of ] and ].]]

DNA was first isolated by the Swiss physician ] who, in 1869, discovered a microscopic substance in the ] of discarded surgical bandages. As it resided in the nuclei of cells, he called it "nuclein".<ref>{{cite journal | vauthors = Miescher F | year = 1871 | url = https://books.google.com/books?id=YJRTAAAAcAAJ&pg=PA441 | title = Ueber die chemische Zusammensetzung der Eiterzellen | language = de | trans-title = On the chemical composition of pus cells | journal = Medicinisch-chemische Untersuchungen | volume = 4 | pages = 441–60 | quote = ''Ich habe mich daher später mit meinen Versuchen an die ganzen Kerne gehalten, die Trennung der Körper, die ich einstweilen ohne weiteres Präjudiz als lösliches und unlösliches Nuclein bezeichnen will, einem günstigeren Material überlassend.'' (Therefore, in my experiments I subsequently limited myself to the whole nucleus, leaving to a more favorable material the separation of the substances, that for the present, without further prejudice, I will designate as soluble and insoluble nuclear material ("Nuclein"))}}</ref><ref>{{cite journal | vauthors = Dahm R | s2cid = 915930 | title = Discovering DNA: Friedrich Miescher and the early years of nucleic acid research | journal = Human Genetics | volume = 122 | issue = 6 | pages = 565–81 | date = January 2008 | pmid = 17901982 | doi = 10.1007/s00439-007-0433-0 }}</ref> In 1878, ] isolated the non-protein component of "nuclein", nucleic acid, and later isolated its five primary ]s.<ref>See:
* {{cite journal | vauthors = Kossel A | year = 1879 | url = https://books.google.com/books?id=4H5NAAAAYAAJ&pg=PA284 | title = Ueber Nucleïn der Hefe | language = de| trans-title = On nuclein in yeast | journal = Zeitschrift für physiologische Chemie | volume = 3 | pages = 284–91 }}
* {{cite journal | vauthors = Kossel A | year = 1880 | url = https://books.google.com/books?id=u4s1AQAAMAAJ&pg=PA290 | title = Ueber Nucleïn der Hefe II | language = de | trans-title = On nuclein in yeast, Part 2 | journal = Zeitschrift für physiologische Chemie | volume = 4 | pages = 290–95 }}
* {{cite journal | vauthors = Kossel A | year = 1881 | url = https://books.google.com/books?id=xYs1AQAAMAAJ&pg=PA267 | title = Ueber die Verbreitung des Hypoxanthins im Thier- und Pflanzenreich | language = de | trans-title = On the distribution of hypoxanthins in the animal and plant kingdoms | journal = Zeitschrift für physiologische Chemie | volume = 5 | pages = 267–71 }}
* {{cite book | vauthors = Kossel A | title = Untersuchungen über die Nucleine und ihre Spaltungsprodukte | language = de | trans-title = Investigations into nuclein and its cleavage products | location = Strassburg, Germany | publisher = K.J. Trübner | year = 1881 | pages = 19 }}
* {{cite journal | vauthors = Kossel A | year = 1882 | url = https://books.google.com/books?id=z4s1AQAAMAAJ&pg=PA422 | title = Ueber Xanthin und Hypoxanthin |trans-title= On xanthin and hypoxanthin | journal = Zeitschrift für physiologische Chemie | volume = 6 | pages = 422–31 }}
* Albrect Kossel (1883) {{webarchive|url=https://web.archive.org/web/20171117235430/https://books.google.com/books?id=2os1AQAAMAAJ&pg=PA7 |date=17 November 2017 }} (On the chemistry of the cell nucleus), ''Zeitschrift für physiologische Chemie'', '''7''': 7–22.
* {{cite journal | vauthors = Kossel A | year = 1886 | title = Weitere Beiträge zur Chemie des Zellkerns | language = de | trans-title = Further contributions to the chemistry of the cell nucleus | journal = Zeitschrift für Physiologische Chemie | volume = 10 | pages = 248–64 | url = http://vlp.mpiwg-berlin.mpg.de/library/data/lit16615/index_html?pn=1&ws=1.5 | quote = On p. 264, Kossel remarked presciently: Der Erforschung der quantitativen Verhältnisse der vier stickstoffreichen Basen, der Abhängigkeit ihrer Menge von den physiologischen Zuständen der Zelle, verspricht wichtige Aufschlüsse über die elementaren physiologisch-chemischen Vorgänge. (The study of the quantitative relations of the four nitrogenous bases— of the dependence of their quantity on the physiological states of the cell—promises important insights into the fundamental physiological-chemical processes.) }}</ref><ref name="Yale_Jones_1953">{{cite journal | vauthors = Jones ME | title = Albrecht Kossel, a biographical sketch | journal = The Yale Journal of Biology and Medicine | volume = 26 | issue = 1 | pages = 80–97 | date = September 1953 | pmid = 13103145 | pmc = 2599350 }}</ref>

In 1909, ] identified the base, sugar, and phosphate nucleotide unit of RNA (then named "yeast nucleic acid").<ref>{{cite journal | vauthors = Levene PA, Jacobs WA | year = 1909 | title = Über Inosinsäure | language = de | journal = Berichte der Deutschen Chemischen Gesellschaft | volume = 42 | pages = 1198–203 |url=https://babel.hathitrust.org/cgi/pt?id=iau.31858002459620&view=1up&seq=1054 | doi=10.1002/cber.190904201196}}</ref><ref>{{cite journal | vauthors = Levene PA, Jacobs WA | year = 1909 | title = Über die Hefe-Nucleinsäure | language = de | journal = Berichte der Deutschen Chemischen Gesellschaft | volume = 42 | issue = 2 | pages = 2474–78 | doi=10.1002/cber.190904202148| url = https://zenodo.org/record/2175598 }}</ref><ref>{{cite journal | vauthors = Levene P |title=The structure of yeast nucleic acid| journal=J Biol Chem |volume=40 |issue=2 |pages=415–24 |year=1919|doi=10.1016/S0021-9258(18)87254-4|doi-access=free }}</ref> In 1929, Levene identified deoxyribose sugar in "thymus nucleic acid" (DNA).<ref>{{cite journal | vauthors = Cohen JS, Portugal FH | year = 1974 | title = The search for the chemical structure of DNA | journal = Connecticut Medicine | volume = 38 | issue = 10 | pages = 551–52, 554–57 | pmid = 4609088 | url = https://profiles.nlm.nih.gov/ps/access/CCAAHW.pdf }}</ref> Levene suggested that DNA consisted of a string of four nucleotide units linked together through the phosphate groups ("tetranucleotide hypothesis"). Levene thought the chain was short and the bases repeated in a fixed order. In 1927, ] proposed that inherited traits would be inherited via a "giant hereditary molecule" made up of "two mirror strands that would replicate in a semi-conservative fashion using each strand as a template".<ref>Koltsov proposed that a cell's genetic information was encoded in a long chain of amino acids. See:
* {{cite speech | vauthors = Koltsov HK | title = Физико-химические основы морфологии | trans-title = The physical-chemical basis of morphology | language = ru | event = 3rd All-Union Meeting of Zoologist, Anatomists, and Histologists | location = Leningrad, U.S.S.R. | date = 12 December 1927 }}
* Reprinted in: {{cite journal | vauthors = Koltsov HK | title = Физико-химические основы морфологии | trans-title = The physical-chemical basis of morphology | language = ru| journal = Успехи экспериментальной биологии (Advances in Experimental Biology) series B | volume = 7 | issue = 1 | pages = ? | date = 1928 }}
* Reprinted in German as: {{cite journal | vauthors = Koltzoff NK | date = 1928 | title = Physikalisch-chemische Grundlagen der Morphologie | trans-title = The physical-chemical basis of morphology | language = de | journal = Biologisches Zentralblatt | volume = 48 | issue = 6 | pages = 345–69 }}
* In 1934, Koltsov contended that the proteins that contain a cell's genetic information replicate. See: {{cite journal | vauthors = Koltzoff N | title = The structure of the chromosomes in the salivary glands of Drosophila | journal = Science | volume = 80 | issue = 2075 | pages = 312–13 | date = October 1934 | pmid = 17769043 | doi = 10.1126/science.80.2075.312 | quote = From page 313: "I think that the size of the chromosomes in the salivary glands is determined through the multiplication of ''genonemes''. By this term I designate the axial thread of the chromosome, in which the geneticists locate the linear combination of genes; … In the normal chromosome there is usually only one genoneme; before cell-division this genoneme has become divided into two strands."| bibcode = 1934Sci....80..312K }}</ref><ref name="Soyfer">{{cite journal | vauthors = Soyfer VN | s2cid = 46277758 | title = The consequences of political dictatorship for Russian science | journal = Nature Reviews Genetics | volume = 2 | issue = 9 | pages = 723–29 | date = September 2001 | pmid = 11533721 | doi = 10.1038/35088598 }}</ref> In 1928, ] in his ] discovered that ] of the "smooth" form of ''Pneumococcus'' could be transferred to the "rough" form of the same bacteria by mixing killed "smooth" bacteria with the live "rough" form.<ref>{{cite journal | vauthors = Griffith F | title = The Significance of Pneumococcal Types | journal = The Journal of Hygiene | volume = 27 | issue = 2 | pages = 113–59 | date = January 1928 | pmid = 20474956 | pmc = 2167760 | doi = 10.1017/S0022172400031879 }}</ref><ref>{{cite journal | vauthors = Lorenz MG, Wackernagel W | title = Bacterial gene transfer by natural genetic transformation in the environment | journal = Microbiological Reviews | volume = 58 | issue = 3 | pages = 563–602 | date = September 1994 | pmid = 7968924 | pmc = 372978 | doi = 10.1128/MMBR.58.3.563-602.1994 }}</ref> This system provided the first clear suggestion that DNA carries genetic information.

In 1933, while studying virgin ] eggs, ] suggested that DNA is found in the ] and that ] is present exclusively in the ]. At the time, "yeast nucleic acid" (RNA) was thought to occur only in plants, while "thymus nucleic acid" (DNA) only in animals. The latter was thought to be a tetramer, with the function of buffering cellular pH.<ref>{{cite journal | vauthors = Brachet J | year = 1933 | title = Recherches sur la synthese de l'acide thymonucleique pendant le developpement de l'oeuf d'Oursin | language = it | journal = Archives de Biologie | volume = 44 | pages = 519–76 }}</ref><ref>{{cite book | vauthors = Burian R | year = 1994 | chapter = Jean Brachet's Cytochemical Embryology: Connections with the Renovation of Biology in France? | veditors = Debru C, Gayon J, Picard JF | title = Les sciences biologiques et médicales en France 1920–1950 | volume = 2 | series = Cahiers pour I'histoire de la recherche | location = Paris | publisher = CNRS Editions | pages = 207–20 | chapter-url = http://www.histcnrs.fr/ColloqDijon/Burian-Brachet.pdf }}</ref>

In 1937, ] produced the first X-ray diffraction patterns that showed that DNA had a regular structure.<ref>See:
* {{cite journal | vauthors = Astbury WT, Bell FO | year = 1938 | title = Some recent developments in the X-ray study of proteins and related structures | journal = Cold Spring Harbor Symposia on Quantitative Biology | volume = 6 | pages = 109–21 | url = http://www.leeds.ac.uk/heritage/Astbury/bibliography/CSHSQB_Astbury_and_Bell_1938.pdf | archive-url = https://web.archive.org/web/20140714204539/http://www.leeds.ac.uk/heritage/Astbury/bibliography/CSHSQB_Astbury_and_Bell_1938.pdf | archive-date = 14 July 2014 | doi=10.1101/sqb.1938.006.01.013}}
* {{cite journal | vauthors = Astbury WT | title = X-ray studies of nucleic acids | journal = Symposia of the Society for Experimental Biology | issue = 1 | pages = 66–76 | year = 1947 | pmid = 20257017 | url = http://scarc.library.oregonstate.edu/coll/pauling/dna/papers/astbury-xray.html | archive-url = https://web.archive.org/web/20140705132403/http://scarc.library.oregonstate.edu/coll/pauling/dna/papers/astbury-xray.html | archive-date=5 July 2014 }}</ref>

In 1943, ], along with co-workers ] and ], identified DNA as the ], supporting Griffith's suggestion (]).<ref>{{cite journal | vauthors = Avery OT, Macleod CM, McCarty M | title = Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types: Induction of Transformation by a Desoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III | journal = The Journal of Experimental Medicine | volume = 79 | issue = 2 | pages = 137–158 | date = February 1944 | pmid = 19871359 | pmc = 2135445 | doi = 10.1084/jem.79.2.137 }}</ref> ] developed and published observations now known as ], stating that in DNA from any species of any organism, the amount of ] should be equal to ] and the amount of ] should be equal to ].<ref name="chargaff_1950">{{cite journal | vauthors = Chargaff E | title = Chemical specificity of nucleic acids and mechanism of their enzymatic degradation | journal = Experientia | volume = 6 | issue = 6 | pages = 201–209 | date = June 1950 | pmid = 15421335 | doi = 10.1007/BF02173653 | s2cid = 2522535 }}</ref><ref name="kresge_2005">{{cite journal | vauthors = Kresge N, Simoni RD, Hill RL |title=Chargaff's Rules: the Work of Erwin Chargaff |journal=Journal of Biological Chemistry |date=June 2005 |volume=280 |issue=24 |pages=172–174 |doi=10.1016/S0021-9258(20)61522-8|doi-access=free }}</ref>

] outside ] ] in Cambridge, England commemorating Crick and Watson]]

Late in 1951, ] started working with ] at the ] within the ]. DNA's role in ] was confirmed in 1952 when ] and ] in the ] showed that DNA is the ] of the ].<ref>{{cite journal | vauthors = Hershey AD, Chase M | title = Independent functions of viral protein and nucleic acid in growth of bacteriophage | journal = The Journal of General Physiology | volume = 36 | issue = 1 | pages = 39–56 | date = May 1952 | pmid = 12981234 | pmc = 2147348 | doi = 10.1085/jgp.36.1.39 }}</ref>
]
In May 1952, ], a graduate student working under the supervision of ], took an ] image, labeled as "]",<ref>{{Cite web|title=Pictures and Illustrations: Crystallographic photo of Sodium Thymonucleate, Type B. "Photo 51." May 1952|url=http://scarc.library.oregonstate.edu/coll/pauling/dna/pictures/sci9.001.5.html|access-date=2023-05-18|website=scarc.library.oregonstate.edu}}</ref> at high hydration levels of DNA. This photo was given to Watson and Crick by ] and was critical to their obtaining the correct structure of DNA. Franklin told Crick and Watson that the backbones had to be on the outside. Before then, Linus Pauling, and Watson and Crick, had erroneous models with the chains inside and the bases pointing outwards. Franklin's identification of the ] for DNA crystals revealed to Crick that the two DNA strands were ].<ref name="ReferenceA">{{cite book| vauthors = Schwartz J |title=In pursuit of the gene: from Darwin to DNA |url= https://archive.org/details/inpursuitofgenef00schw |url-access=registration |year=2008|publisher=Harvard University Press|location=Cambridge, Mass.|isbn=978-0-674-02670-4 }}</ref> In February 1953, ] and ] proposed a model for nucleic acids containing three intertwined chains, with the phosphates near the axis, and the bases on the outside.<ref name="pmid16578429">{{cite journal | vauthors = Pauling L, Corey RB | title = A Proposed Structure For The Nucleic Acids | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 39 | issue = 2 | pages = 84–97 | date = February 1953 | pmid = 16578429 | pmc = 1063734 | doi = 10.1073/pnas.39.2.84| url = http://scarc.library.oregonstate.edu/coll/pauling/dna/papers/1953p.9-084.html | bibcode = 1953PNAS...39...84P | doi-access = free }}</ref> Watson and Crick completed their model, which is now accepted as the first correct model of the double helix of ]. On 28 February 1953 Crick interrupted patrons' lunchtime at ] ] in Cambridge, England to announce that he and Watson had "discovered the secret of life".<ref>{{cite book | vauthors = Regis E | date = 2009 | title = What Is Life?: investigating the nature of life in the age of synthetic biology | location = Oxford | publisher = ] | isbn = 978-0-19-538341-6 | page = 52 }}</ref>

]
The 25 April 1953 issue of the journal '']'' published a series of five articles giving the Watson and Crick double-helix structure DNA and evidence supporting it.<ref name=NatureDNA50>{{cite web | work = Nature Archives | url = http://www.nature.com/nature/dna50/archive.html | title = Double Helix of DNA: 50 Years | archive-url = https://web.archive.org/web/20150405140401/http://www.nature.com/nature/dna50/archive.html | archive-date=5 April 2015 | url-status=dead }}</ref> The structure was reported in a letter titled "''MOLECULAR STRUCTURE OF NUCLEIC ACIDS A Structure for Deoxyribose Nucleic Acid''{{-"}}, in which they said, "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material."<ref name="Watson-1953" /> This letter was followed by a letter from Franklin and Gosling, which was the first publication of their own X-ray diffraction data and of their original analysis method.<ref name=NatFranGos /><ref>{{cite web | url = http://osulibrary.oregonstate.edu/specialcollections/coll/pauling/dna/pictures/franklin-typeBphoto.html | title = Original X-ray diffraction image | publisher = Oregon State Library | access-date = 6 February 2011 | url-status=live | archive-url = https://web.archive.org/web/20090130111849/http://osulibrary.oregonstate.edu/specialcollections/coll/pauling/dna/pictures/franklin-typeBphoto.html | archive-date=30 January 2009 }}</ref> Then followed a letter by Wilkins and two of his colleagues, which contained an analysis of ''in vivo'' B-DNA X-ray patterns, and which supported the presence ''in vivo'' of the Watson and Crick structure.<ref name="NatWilk" />

In April 2023, scientists, based on new evidence, concluded that Rosalind Franklin was a contributor and "equal player" in the discovery process of DNA, rather than otherwise, as may have been presented subsequently after the time of the discovery.<ref name="AP-20230425">{{cite news | vauthors = Burakoff M |title=Rosalind Franklin's role in DNA discovery gets a new twist |url=https://apnews.com/article/dna-double-helix-rosalind-franklin-watson-crick-69ec8164c720e0b23374da69a1d3708d |date=25 April 2023 |work=] |accessdate=25 April 2023 }}</ref><ref name="NYT-20230425">{{cite news | vauthors = Anthes E |title=Untangling Rosalind Franklin's Role in DNA Discovery, 70 Years On – Historians have long debated the role that Dr. Franklin played in identifying the double helix. A new opinion essay argues that she was an "equal contributor." |url=https://www.nytimes.com/2023/04/25/science/rosalind-franklin-dna.html |date=25 April 2023 |work=] |url-status=live |archiveurl=https://archive.today/20230425182515/https://www.nytimes.com/2023/04/25/science/rosalind-franklin-dna.html |archivedate=25 April 2023 |accessdate=26 April 2023 }}</ref><ref name="NAT-202304254">{{cite journal | vauthors = Cobb M, Comfort N |title=What Rosalind Franklin truly contributed to the discovery of DNA's structure – Franklin was no victim in how the DNA double helix was solved. An overlooked letter and an unpublished news article, both written in 1953, reveal that she was an equal player. |date=25 April 2023 |journal=] |volume=616 |issue=7958 |pages=657–660 |doi=10.1038/d41586-023-01313-5 |pmid=37100935 |s2cid=258314143 |doi-access=free |bibcode=2023Natur.616..657C }}</ref>

In 1962, after Franklin's death, Watson, Crick, and Wilkins jointly received the ].<ref>{{cite web | url = http://nobelprize.org/nobel_prizes/medicine/laureates/1962/ | title = The Nobel Prize in Physiology or Medicine 1962 | work = Nobelprize.org }}</ref> Nobel Prizes are awarded only to living recipients. A debate continues about who should receive credit for the discovery.<ref>{{cite journal | vauthors = Maddox B | s2cid = 4428347 | title = The double helix and the 'wronged heroine' | journal = Nature | volume = 421 | issue = 6921 | pages = 407–08 | date = January 2003 | pmid = 12540909 | doi = 10.1038/nature01399 | url = http://www.biomath.nyu.edu/index/course/hw_articles/nature4.pdf | bibcode = 2003Natur.421..407M | url-status=live | archive-url = https://web.archive.org/web/20161017011403/http://www.biomath.nyu.edu/index/course/hw_articles/nature4.pdf | archive-date = 17 October 2016 | df = dmy-all | doi-access = free }}</ref>


In an influential presentation in 1957, Crick laid out the ], which foretold the relationship between DNA, RNA, and proteins, and articulated the "adaptor hypothesis".<ref>{{cite speech | vauthors = Crick FH |title=A Note for the RNA Tie Club | date= 1955 | location = Cambridge, England |url= http://genome.wellcome.ac.uk/assets/wtx030893.pdf | archive-url = https://web.archive.org/web/20081001223217/http://genome.wellcome.ac.uk/assets/wtx030893.pdf | url-status=dead | archive-date = 1 October 2008 }}</ref> Final confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 through the ].<ref>{{cite journal | vauthors = Meselson M, Stahl FW | title = The Replication of DNA in Escherichia Coli | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 44 | issue = 7 | pages = 671–82 | date = July 1958 | pmid = 16590258 | pmc = 528642 | doi = 10.1073/pnas.44.7.671 | bibcode = 1958PNAS...44..671M | doi-access = free }}</ref> Further work by Crick and co-workers showed that the genetic code was based on non-overlapping triplets of bases, called ], allowing ], ], and ] to decipher the genetic code.<ref>{{cite web | url = http://nobelprize.org/nobel_prizes/medicine/laureates/1968/ | title = The Nobel Prize in Physiology or Medicine 1968 | work = Nobelprize.org }}</ref> These findings represent the birth of ].<ref>{{cite journal | vauthors = Pray L | year = 2008 | title = Discovery of DNA structure and function: Watson and Crick. | journal = Nature Education | volume = 1 | issue = 1 | pages = 100 }}</ref>
A DNA helix does not usually interact with other segments of DNA and in human cells the different chromosomes even occupy separate areas in the nucleus called "chromosome territories".<ref>{{cite journal | author = Cremer T, Cremer C | title = Chromosome territories, nuclear architecture and gene regulation in mammalian cells | journal = Nat Rev Genet | volume = 2 | issue = 4 | pages = 292-301 | year = 2001 | id = PMID 11283701}}</ref> This physical separation of different chromosomes is important for the ability of DNA to function as a stable repository for information, as one of the few times chromosomes interact is when they ]. Recombination is when two DNA helices break, swap a section and then rejoin. In eukaryotes this process usually occurs during ], when the two sister ]s are paired together in the center of the cell. Recombination allows chromosomes to exchange genetic information and produces new combinations of genes, which increases the efficiency of ] and can be important in the rapid evolution of new proteins.<ref>{{cite journal | author = Pál C, Papp B, Lercher M | title = An integrated view of protein evolution | journal = Nat Rev Genet | volume = 7 | issue = 5 | pages = 337-48 | year = 2006 | id = PMID 16619049}}</ref> Genetic recombination can also be involved in DNA repair, particularly in the cell's response to double-strand breaks.<ref>{{cite journal | author = O'Driscoll M, Jeggo P | title = The role of double-strand break repair - insights from human genetics | journal = Nat Rev Genet | volume = 7 | issue = 1 | pages = 45-54 | year = 2006 | id = PMID 16369571}}</ref>
{{clear}}


In 1986, DNA analysis was first used for criminal investigative purposes when police in the UK requested ] of the University of Leicester to verify or disprove a suspect's rape-murder "confession". In this particular case, the suspect had confessed to two rape-murders, but had later retracted his confession. DNA testing at the university labs soon disproved the veracity of the suspect's original "confession", and the suspect was exonerated from the murder-rape charges.<ref>{{cite journal | pmc=3561883 | year=2003 | vauthors=Panneerchelvam S, Norazmi MN | title=Forensic DNA Profiling and Database | journal=The Malaysian Journal of Medical Sciences | volume=10 | issue=2 | pages=20–26 | pmid=23386793 }}</ref>
The most common form of recombination is ], where the two chromosomes involved share very similar sequences. Non-homologous recombination can be damaging to cells, as it can produce ]s and genetic abnormalities. The recombination reaction is catalyzed by enzymes known as ''recombinases'', such as ].<ref>{{cite journal | author = Ghosh K, Van Duyne G | title = Cre-loxP biochemistry | journal = Methods | volume = 28 | issue = 3 | pages = 374-83 | year = 2002 | id = PMID 12431441}}</ref> In the first step, the recombinase creates a nick in one strand of a DNA double helix, allowing the nicked strand to pull apart from its ] strand and ] to one strand of the double helix on the opposite chromatid. A second nick allows the strand in the second chromatid to pull apart and anneal to the remaining strand in the first helix, forming a structure known as a ''cross-strand exchange'' or a ]. The Holliday junction is a tetrahedral junction structure which can be moved along the pair of chromosomes, swapping one strand for another. The recombination reaction is then halted by cleavage of the junction and re-ligation of the released DNA.<ref>{{cite journal | author = Dickman M, Ingleston S, Sedelnikova S, Rafferty J, Lloyd R, Grasby J, Hornby D | title = The RuvABC resolvasome | journal = Eur J Biochem | volume = 269 | issue = 22 | pages = 5492-501 | year = 2002 | id = PMID 12423347}}</ref>


==Uses in technology== == See also ==
{{Div col}}
===Forensics ===
* {{annotated link|Autosome}}
{{further|]}}
* {{annotated link|Crystallography}}
* {{annotated link|DNA Day}}
* {{annotated link|DNA microarray}}
* {{annotated link|DNA sequencing}}
* {{annotated link|Genetic disorder}}
* {{annotated link|Genetic genealogy}}
* {{annotated link|Haplotype}}
* {{annotated link|Meiosis}}
* {{annotated link|Nucleic acid notation}}
* {{annotated link|Nucleic acid sequence}}
* {{annotated link|Ribosomal DNA}}
* {{annotated link|Southern blot}}
* {{annotated link|X-ray scattering techniques}}
* {{annotated link|Xeno nucleic acid}}
{{Div col end}}


== References ==
] can use DNA in ], ], ], ] or ] at a crime scene to identify a perpetrator. This process is called ] or more accurately, DNA profiling. In DNA profiling, the lengths of variable sections of repetitive DNA, such as ] and ]s, are compared between people. This method is usually an extremely reliable technique for identifying a criminal.<ref>{{cite journal | author = Collins A, Morton N | title = Likelihood ratios for DNA identification | url=http://www.pnas.org/cgi/reprint/91/13/6007.pdf | journal = Proc Natl Acad Sci U S A | volume = 91 | issue = 13 | pages = 6007-11 | year = 1994 | id = PMID 8016106}}</ref> However, identification can be complicated if the scene is contaminated with DNA from several people.<ref>{{cite journal | author = Weir B, Triggs C, Starling L, Stowell L, Walsh K, Buckleton J | title = Interpreting DNA mixtures | journal = J Forensic Sci | volume = 42 | issue = 2 | pages = 213-22 | year = 1997 | id = PMID 9068179}}</ref> DNA profiling was developed in 1984 by British geneticist Sir ],<ref>{{cite journal | author = Jeffreys A, Wilson V, Thein S | title = Individual-specific 'fingerprints' of human DNA. | journal = Nature | volume = 316 | issue = 6023 | pages = 76-9 | year = | id = PMID 2989708}}</ref> and first used in forensic science to convict Colin Pitchfork in the 1988 ] case.<ref> Forensic Science Service Accessed 23 Dec 2006</ref> People convicted of certain types of crimes may be required to provide a sample of DNA for a database. This has helped investigators solve old cases where only a DNA sample was obtained from the scene. DNA profiling can also be used to identify victims of mass casualty incidents.<ref>{{cite web |url=http://massfatality.dna.gov/Introduction/ |title=DNA Identification in Mass Fatality Incidents |date=September 2006 |publisher=National Institute of Justice}}</ref>
{{Reflist|refs =


<ref name="Birney_2007">{{cite journal |author-link2=John Stamatoyannopoulos | vauthors = Birney E, Stamatoyannopoulos JA, Dutta A, Guigó R, Gingeras TR, Margulies EH, Weng Z, Snyder M, Dermitzakis ET, Thurman RE, Kuehn MS, Taylor CM, Neph S, Koch CM, Asthana S, Malhotra A, Adzhubei I, Greenbaum JA, Andrews RM, Flicek P, Boyle PJ, Cao H, Carter NP, Clelland GK, Davis S, Day N, Dhami P, Dillon SC, Dorschner MO, Fiegler H, Giresi PG, Goldy J, Hawrylycz M, Haydock A, Humbert R, James KD, Johnson BE, Johnson EM, Frum TT, Rosenzweig ER, Karnani N, Lee K, Lefebvre GC, Navas PA, Neri F, Parker SC, Sabo PJ, Sandstrom R, Shafer A, Vetrie D, Weaver M, Wilcox S, Yu M, Collins FS, Dekker J, Lieb JD, Tullius TD, Crawford GE, Sunyaev S, Noble WS, Dunham I, Denoeud F, Reymond A, Kapranov P, Rozowsky J, Zheng D, Castelo R, Frankish A, Harrow J, Ghosh S, Sandelin A, Hofacker IL, Baertsch R, Keefe D, Dike S, Cheng J, Hirsch HA, Sekinger EA, Lagarde J, Abril JF, Shahab A, Flamm C, Fried C, Hackermüller J, Hertel J, Lindemeyer M, Missal K, Tanzer A, Washietl S, Korbel J, Emanuelsson O, Pedersen JS, Holroyd N, Taylor R, Swarbreck D, Matthews N, Dickson MC, Thomas DJ, Weirauch MT, Gilbert J, Drenkow J, Bell I, Zhao X, Srinivasan KG, Sung WK, Ooi HS, Chiu KP, Foissac S, Alioto T, Brent M, Pachter L, Tress ML, Valencia A, Choo SW, Choo CY, Ucla C, Manzano C, Wyss C, Cheung E, Clark TG, Brown JB, Ganesh M, Patel S, Tammana H, Chrast J, Henrichsen CN, Kai C, Kawai J, Nagalakshmi U, Wu J, Lian Z, Lian J, Newburger P, Zhang X, Bickel P, Mattick JS, Carninci P, Hayashizaki Y, Weissman S, Hubbard T, Myers RM, Rogers J, Stadler PF, Lowe TM, Wei CL, Ruan Y, Struhl K, Gerstein M, Antonarakis SE, Fu Y, Green ED, Karaöz U, Siepel A, Taylor J, Liefer LA, Wetterstrand KA, Good PJ, Feingold EA, Guyer MS, Cooper GM, Asimenos G, Dewey CN, Hou M, Nikolaev S, Montoya-Burgos JI, Löytynoja A, Whelan S, Pardi F, Massingham T, Huang H, Zhang NR, Holmes I, Mullikin JC, Ureta-Vidal A, Paten B, Seringhaus M, Church D, Rosenbloom K, Kent WJ, Stone EA, Batzoglou S, Goldman N, Hardison RC, Haussler D, Miller W, Sidow A, Trinklein ND, Zhang ZD, Barrera L, Stuart R, King DC, Ameur A, Enroth S, Bieda MC, Kim J, Bhinge AA, Jiang N, Liu J, Yao F, Vega VB, Lee CW, Ng P, Shahab A, Yang A, Moqtaderi Z, Zhu Z, Xu X, Squazzo S, Oberley MJ, Inman D, Singer MA, Richmond TA, Munn KJ, Rada-Iglesias A, Wallerman O, Komorowski J, Fowler JC, Couttet P, Bruce AW, Dovey OM, Ellis PD, Langford CF, Nix DA, Euskirchen G, Hartman S, Urban AE, Kraus P, Van Calcar S, Heintzman N, Kim TH, Wang K, Qu C, Hon G, Luna R, Glass CK, Rosenfeld MG, Aldred SF, Cooper SJ, Halees A, Lin JM, Shulha HP, Zhang X, Xu M, Haidar JN, Yu Y, Ruan Y, Iyer VR, Green RD, Wadelius C, Farnham PJ, Ren B, Harte RA, Hinrichs AS, Trumbower H, Clawson H, Hillman-Jackson J, Zweig AS, Smith K, Thakkapallayil A, Barber G, Kuhn RM, Karolchik D, Armengol L, Bird CP, de Bakker PI, Kern AD, Lopez-Bigas N, Martin JD, Stranger BE, Woodroffe A, Davydov E, Dimas A, Eyras E, Hallgrímsdóttir IB, Huppert J, Zody MC, Abecasis GR, Estivill X, Bouffard GG, Guan X, Hansen NF, Idol JR, Maduro VV, Maskeri B, McDowell JC, Park M, Thomas PJ, Young AC, Blakesley RW, Muzny DM, Sodergren E, Wheeler DA, Worley KC, Jiang H, Weinstock GM, Gibbs RA, Graves T, Fulton R, Mardis ER, Wilson RK, Clamp M, Cuff J, Gnerre S, Jaffe DB, Chang JL, Lindblad-Toh K, Lander ES, Koriabine M, Nefedov M, Osoegawa K, Yoshinaga Y, Zhu B, de Jong PJ | display-authors = 6 | title = Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project | journal = Nature | volume = 447 | issue = 7146 | pages = 799–816 | date = June 2007 | pmid = 17571346 | pmc = 2212820 | doi = 10.1038/nature05874 | bibcode = 2007Natur.447..799B }}</ref>
===Bioinformatics===
{{further|]}}
] involves the manipulation, searching, and ] DNA sequence data. The development of techniques to store and search DNA sequences have led to widely-applied advances in ], especially ]s, ] and ].<ref>Baldi, Pierre. Brunak, Soren. ''Bioinformatics: The Machine Learning Approach'' MIT Press (2001) ISBN 978-0-262-02506-5</ref> String searching or matching algorithms, which find an occurrence of a sequence of letters inside a larger sequence of letters, was developed to search for specific sequences of nucleotides.<ref>Gusfield, Dan. ''Algorithms on Strings, Trees, and Sequences: Computer Science and Computational Biology''. Cambridge University Press, 15 January ]. ISBN 978-0-521-58519-4.</ref> In other applications such as ]s, even simple algorithms for this problem usually suffice, but DNA sequences cause these algorithms to exhibit near-worst-case behaviour due to their small number of distinct characters. The related problem of ] aims to identify ] sequences and locate the specific ]s that make them distinct. These techniques, especially ], are used in studying ] relationships and ] function.<ref>{{cite journal | author = Sjölander K | title = Phylogenomic inference of protein molecular function: advances and challenges | url=http://bioinformatics.oxfordjournals.org/cgi/reprint/20/2/170 | journal = Bioinformatics | volume = 20 | issue = 2 | pages = 170-9 | year = 2004 | id = PMID 14734307}}</ref> Data sets representing entire genomes' worth of DNA sequences, such as those produced by the ], are difficult to use without annotations, which label the locations of genes and regulatory elements on each chromosome. Regions of DNA sequence that have the characteristic patterns associated with protein- or RNA-coding genes can be identified by ] algorithms, which allow researchers to predict the presence of particular ]s in an organism even before they have been isolated experimentally.<ref name="Mount">{{cite book|author = Mount DM | title = Bioinformatics: Sequence and Genome Analysis | edition = 2 | publisher = Cold Spring Harbor Laboratory Press | location | Cold Spring Harbor, NY | date = 2004 | isbn = 0879697121}}</ref>


<ref name="Gregory_2006">{{cite journal | vauthors = Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E | display-authors = 6 | title = The DNA sequence and biological annotation of human chromosome 1 | journal = Nature | volume = 441 | issue = 7091 | pages = 315–21 | date = May 2006 | pmid = 16710414 | doi = 10.1038/nature04727 | bibcode = 2006Natur.441..315G | doi-access = free }}</ref>
===DNA and computation ===
{{further|]}}
DNA was first used in computing to solve a small version of the directed ], an ] problem.<ref>{{cite journal | author = Adleman L | title = Molecular computation of solutions to combinatorial problems | journal = Science | volume = 266 | issue = 5187 | pages = 1021-4 | year = 1994 | id = PMID 7973651}}</ref> ] is advantageous over electronic computers in power use, space use, and efficiency, due to its ability to compute in a highly parallel fashion (see ]). A number of other problems, including simulation of various ]s, the ], and the bounded version of the ], have since been analysed using DNA computing.<ref>{{cite journal | author = Parker J | title = Computing with DNA. | url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=12524509 | journal = EMBO Rep | volume = 4 | issue = 1 | pages = 7-10 | year = 2003 | id = PMID 12524509}}</ref> Due to its compactness, DNA also has a theoretical role in ], where in particular it allows unbreakable ]s to be efficiently constructed and used.<ref>Ashish Gehani, Thomas LaBean and John Reif. .
Proceedings of the 5th DIMACS Workshop on DNA Based Computers, Cambridge, MA, USA, 14 – 15 June 1999.</ref>


<ref name="Venter_2001">{{cite journal | vauthors = Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N, Levine AJ, Roberts RJ, Simon M, Slayman C, Hunkapiller M, Bolanos R, Delcher A, Dew I, Fasulo D, Flanigan M, Florea L, Halpern A, Hannenhalli S, Kravitz S, Levy S, Mobarry C, Reinert K, Remington K, Abu-Threideh J, Beasley E, Biddick K, Bonazzi V, Brandon R, Cargill M, Chandramouliswaran I, Charlab R, Chaturvedi K, Deng Z, Di Francesco V, Dunn P, Eilbeck K, Evangelista C, Gabrielian AE, Gan W, Ge W, Gong F, Gu Z, Guan P, Heiman TJ, Higgins ME, Ji RR, Ke Z, Ketchum KA, Lai Z, Lei Y, Li Z, Li J, Liang Y, Lin X, Lu F, Merkulov GV, Milshina N, Moore HM, Naik AK, Narayan VA, Neelam B, Nusskern D, Rusch DB, Salzberg S, Shao W, Shue B, Sun J, Wang Z, Wang A, Wang X, Wang J, Wei M, Wides R, Xiao C, Yan C, Yao A, Ye J, Zhan M, Zhang W, Zhang H, Zhao Q, Zheng L, Zhong F, Zhong W, Zhu S, Zhao S, Gilbert D, Baumhueter S, Spier G, Carter C, Cravchik A, Woodage T, Ali F, An H, Awe A, Baldwin D, Baden H, Barnstead M, Barrow I, Beeson K, Busam D, Carver A, Center A, Cheng ML, Curry L, Danaher S, Davenport L, Desilets R, Dietz S, Dodson K, Doup L, Ferriera S, Garg N, Gluecksmann A, Hart B, Haynes J, Haynes C, Heiner C, Hladun S, Hostin D, Houck J, Howland T, Ibegwam C, Johnson J, Kalush F, Kline L, Koduru S, Love A, Mann F, May D, McCawley S, McIntosh T, McMullen I, Moy M, Moy L, Murphy B, Nelson K, Pfannkoch C, Pratts E, Puri V, Qureshi H, Reardon M, Rodriguez R, Rogers YH, Romblad D, Ruhfel B, Scott R, Sitter C, Smallwood M, Stewart E, Strong R, Suh E, Thomas R, Tint NN, Tse S, Vech C, Wang G, Wetter J, Williams S, Williams M, Windsor S, Winn-Deen E, Wolfe K, Zaveri J, Zaveri K, Abril JF, Guigó R, Campbell MJ, Sjolander KV, Karlak B, Kejariwal A, Mi H, Lazareva B, Hatton T, Narechania A, Diemer K, Muruganujan A, Guo N, Sato S, Bafna V, Istrail S, Lippert R, Schwartz R, Walenz B, Yooseph S, Allen D, Basu A, Baxendale J, Blick L, Caminha M, Carnes-Stine J, Caulk P, Chiang YH, Coyne M, Dahlke C, Mays A, Dombroski M, Donnelly M, Ely D, Esparham S, Fosler C, Gire H, Glanowski S, Glasser K, Glodek A, Gorokhov M, Graham K, Gropman B, Harris M, Heil J, Henderson S, Hoover J, Jennings D, Jordan C, Jordan J, Kasha J, Kagan L, Kraft C, Levitsky A, Lewis M, Liu X, Lopez J, Ma D, Majoros W, McDaniel J, Murphy S, Newman M, Nguyen T, Nguyen N, Nodell M, Pan S, Peck J, Peterson M, Rowe W, Sanders R, Scott J, Simpson M, Smith T, Sprague A, Stockwell T, Turner R, Venter E, Wang M, Wen M, Wu D, Wu M, Xia A, Zandieh A, Zhu X | display-authors = 6 | title = The sequence of the human genome | journal = Science | volume = 291 | issue = 5507 | pages = 1304–51 | date = February 2001 | pmid = 11181995 | doi = 10.1126/science.1058040 | bibcode = 2001Sci...291.1304V | doi-access = free }}</ref>
===History and anthropology===
{{further|]}}
Because DNA collects mutations over time, which are then inherited, it contains historical information and by comparing DNA sequences, geneticists can infer the evolutionary history of organisms, their ].<ref>{{cite journal | author = Wray G | title = Dating branches on the tree of life using DNA | url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=11806830 | journal = Genome Biol | volume = 3 | issue = 1 | pages = REVIEWS0001 | year = 2002 | id = PMID 11806830}}</ref> This field of ] is a powerful tool in ]. If DNA sequences within a species are compared, ] can learn the history of particular populations. This can be used in studies ranging from ] to ], for example, DNA evidence is being used to try to identify the ].<ref>''Lost Tribes of Israel'', ], PBS airdate: 22 February 2000. Transcript available from (last accessed on 4 March 2006)</ref><ref>Kleiman, Yaakov. ''aish.com'' (January 13, 2000). Accessed 4 March 2006.</ref>


}}
DNA has also been used to look at modern family relationships, such as establishing family relationships between the descendants of ] and ]. This usage is closely related to the use of DNA in criminal investigations detailed above. Indeed, some criminal investigations have been solved when DNA from crime scenes has matched relatives of the guilty individual.<ref>Bhattacharya, Shaoni. ''newscientist.com'' (20 April 2004). Accessed 22 Dec 06</ref>


== Further reading ==
==History==
{{refbegin}}
] in the ] at the ].]]
* {{cite book | vauthors = Berry A, Watson J | author-link2 = James Watson | name-list-style = vanc | title = DNA: the secret of life | publisher = Alfred A. Knopf | location = New York | year = 2003 | isbn = 0-375-41546-7 | url = https://archive.org/details/dnasecretoflife00wats }}
{{further|]}}
* {{cite book |title=Understanding DNA: the molecule & how it works | vauthors = Calladine CR, Drew HR, Luisi BF, Travers AA | year = 2003 |publisher=Elsevier Academic Press |location=Amsterdam |isbn=0-12-155089-3}}
DNA was first isolated by ] who discovered a substance he called "nuclein" in 1869.<ref>{{cite journal | author = Dahm R | title = Friedrich Miescher and the discovery of DNA | journal = Dev Biol | volume = 278 | issue = 2 | pages = 274-88 | year = 2005 | id = PMID 15680349}}</ref> In 1929 this discovery was followed by ]'s identification of the base, sugar and phosphate nucleotide unit.<ref>{{cite journal | author = Levene P, | title = The structure of yeast nucleic acid | url=http://www.jbc.org/cgi/reprint/40/2/415 | journal = J Biol Chem | volume = 40 | issue = 2 | pages = 415-24 | year = 1919}}</ref> Levene suggested that DNA consisted of a string of nucleotide units linked together through the phosphate groups. However Levene thought the chain was short and the bases repeated in a fixed order. In 1937 ] produced the first ] patterns that showed that DNA had a regular structure.<ref>{{cite journal | author =Astbury W, | title = Nucleic acid | journal = Symp. SOC. Exp. Bbl | volume = 1 | issue = 66 | year = 1947}}</ref>
* {{cite book | vauthors = Carina D, Clayton J | title = 50 years of DNA | publisher = Palgrave Macmillan | location = Basingstoke | year = 2003 | isbn = 1-4039-1479-6 | url = https://archive.org/details/50yearsofdna00clay }}
* {{cite book | author-link = Horace Freeland Judson | vauthors = Judson HF | date = 1979 | title = The Eighth Day of Creation: Makers of the Revolution in Biology | isbn = 0-671-22540-5 | edition = 2nd | publisher = Cold Spring Harbor Laboratory Press }}
* {{cite book | vauthors = Olby RC | author-link = Robert Olby | title = The path to the double helix: the discovery of DNA |publisher=Dover Publications |location=New York |year=1994 |isbn=0-486-68117-3}} First published in October 1974 by MacMillan, with foreword by Francis Crick; the definitive DNA textbook, revised in 1994 with a nine-page postscript.
* {{cite journal | vauthors = Olby R | title = Quiet debut for the double helix | journal = Nature | volume = 421 | issue = 6921 | pages = 402–05 | date = January 2003 | pmid = 12540907 | doi = 10.1038/nature01397 | author-link = Robert Olby | bibcode = 2003Natur.421..402O | doi-access = free }}
* {{cite book | vauthors = Olby RC | title=Francis Crick: A Biography |publisher=Cold Spring Harbor Laboratory Press |location=Plainview, N.Y |year=2009 |isbn=978-0-87969-798-3}}
* {{cite book | vauthors = Micklas D | date = 2003 | title = DNA Science: A First Course | publisher = Cold Spring Harbor Press | isbn = 978-0-87969-636-8 }}
* {{cite book | vauthors = Ridley M | author-link = Matt Ridley |title=Francis Crick: discoverer of the genetic code |publisher=Eminent Lives, Atlas Books |location=Ashland, OH |year=2006 |isbn=0-06-082333-X}}
* {{cite book | vauthors = Rosenfeld I | date = 2010 | title = DNA: A Graphic Guide to the Molecule that Shook the World | publisher = Columbia University Press | isbn = 978-0-231-14271-7 }}
* {{cite book | vauthors = Schultz M, Cannon Z | date = 2009 | title = The Stuff of Life: A Graphic Guide to Genetics and DNA | url = https://archive.org/details/stuffoflifegraph00schu | url-access = registration | publisher = Hill and Wang | isbn = 978-0-8090-8947-5 }}
* {{cite book | author-link1 = Gunther Stent | vauthors = Stent GS, Watson J |title=The Double Helix: A Personal Account of the Discovery of the Structure of DNA | url = https://archive.org/details/doublehelixpers00wats_0 | url-access = registration |publisher=Norton |location=New York |year=1980 |isbn=0-393-95075-1}}
* {{cite book | vauthors = Watson J | date = 2004 | title = DNA: The Secret of Life | publisher = Random House | isbn = 978-0-09-945184-6 }}
* {{cite book | author-link = Maurice Wilkins | vauthors = Wilkins M |title=The third man of the double helix the autobiography of Maurice Wilkins |publisher=University Press |location=Cambridge, England |year=2003 |isbn=0-19-860665-6}}
{{refend}}


== External links ==
In 1943, ] discovered that traits of the "smooth" form of the ''Pneumococcus'' could be transferred to the "rough" form of the same bacteria by mixing killed "smooth" bacteria with the live "rough" form. Avery identified DNA as this ].<ref>{{cite journal | author = Avery O, MacLeod C, McCarty M | title = Studies on the chemical nature of the substance inducing transformation of pneumococcal types. Inductions of transformation by a desoxyribonucleic acid fraction isolated from pneumococcus type III | url=http://www.jem.org/cgi/reprint/149/2/297 | journal = J Exp Med | volume = 149 | issue = 2 | pages = 297-326 | year = 1979 | id = PMID 33226}}</ref> DNA's role in heredity was confirmed in 1953, when ] and ] in the ], showed that DNA is is the ] of the ].<ref>{{cite journal | author = Hershey A, Chase M | title = Independent functions of viral protein and nucleic acid in growth of bacteriophage | url=http://www.jgp.org/cgi/reprint/36/1/39.pdf | journal = J Gen Physiol | volume = 36 | issue = 1 | pages = 39-56 | year = 1952 | id = PMID 12981234}}</ref>
{{Library resources box
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{{Spoken Misplaced Pages|dna.ogg|date=12 February 2007}}
*
* From the official Nobel Prize web site
*
*
* , '']''
* {{Proteopedia|DNA}}
* {{Proteopedia|Forms_of_DNA}}
* ENCODE home page at ]
* National Centre for Biotechnology Education
* – ''DNA from the Beginning'' Study Guide
* {{PDB Molecule of the Month|23|DNA}}
* . '']'', June 1953. First American newspaper coverage of the discovery of the DNA structure
* Another DNA Learning Center site on DNA, genes, and heredity from Mendel to the human genome project.
* at Mandeville Special Collections Library, ]
* See , Nature, 5 April 2013.


{{Genetics}}
Using ] data from ] and the information that the bases were paired, ] and ] produced the first accurate model of DNA structure in 1953 in their article ].<ref name=Watson/> Watson and Crick proposed the ] of molecular biology in 1957, describing how proteins are produced from ] DNA. In 1962 Watson, Crick, and ] jointly received the ].<ref> Nobelprize.org Accessed 22 Dec 06</ref>
{{Gene expression}}
{{Nucleic acids}}
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]
In an influential presentation in 1957, Crick laid out the "]", which foretold the relationship between DNA, RNA, and proteins, and articulated the "adaptor hypothesis".<ref>Crick, F.H.C. genome.wellcome.ac.uk (Lecture, 1955). Accessed 22 Dec 2006</ref> Final confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 through the ].<ref>{{cite journal | author = Meselson M, Stahl F | title = The replication of DNA in Escherichia coli | journal = Proc Natl Acad Sci U S A | volume = 44 | issue = 7 | pages = 671-82 | year = 1958 | id = PMID 16590258}}</ref> Further work by Crick and coworkers showed that the genetic code was based on non-overlapping triplets of bases, called codons, allowing ], ] and ] to decipher the ].<ref> Nobelprize.org Accessed 22 Dec 06</ref> These findings represent the birth of ].
]
]
]

Latest revision as of 18:18, 22 December 2024

Molecule that carries genetic information

For a non-technical introduction to the topic, see Introduction to genetics. For other uses, see DNA (disambiguation).

A chromosome unravelling into a long string of DNA, a section of which is highlighted as the gene Chromosome (10 - 10 bp) DNA Gene (10 - 10 bp ) Function The image above contains clickable linksA chromosome and its packaged long strand of DNA unraveled. The DNA's base pairs encode genes, which provide functions. A human DNA can have up to 500 million base pairs with thousands of genes.
The structure of the DNA double helix (type B-DNA). The atoms in the structure are colour-coded by element and the detailed structures of two base pairs are shown in the bottom right.
Simplified diagram
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Deoxyribonucleic acid (/diːˈɒksɪˌraɪboʊnjuːˌkliːɪk, -ˌkleɪ-/ ; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of all known organisms and many viruses. DNA and ribonucleic acid (RNA) are nucleic acids. Alongside proteins, lipids and complex carbohydrates (polysaccharides), nucleic acids are one of the four major types of macromolecules that are essential for all known forms of life.

The two DNA strands are known as polynucleotides as they are composed of simpler monomeric units called nucleotides. Each nucleotide is composed of one of four nitrogen-containing nucleobases (cytosine , guanine , adenine or thymine ), a sugar called deoxyribose, and a phosphate group. The nucleotides are joined to one another in a chain by covalent bonds (known as the phosphodiester linkage) between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone. The nitrogenous bases of the two separate polynucleotide strands are bound together, according to base pairing rules (A with T and C with G), with hydrogen bonds to make double-stranded DNA. The complementary nitrogenous bases are divided into two groups, the single-ringed pyrimidines and the double-ringed purines. In DNA, the pyrimidines are thymine and cytosine; the purines are adenine and guanine.

Both strands of double-stranded DNA store the same biological information. This information is replicated when the two strands separate. A large part of DNA (more than 98% for humans) is non-coding, meaning that these sections do not serve as patterns for protein sequences. The two strands of DNA run in opposite directions to each other and are thus antiparallel. Attached to each sugar is one of four types of nucleobases (or bases). It is the sequence of these four nucleobases along the backbone that encodes genetic information. RNA strands are created using DNA strands as a template in a process called transcription, where DNA bases are exchanged for their corresponding bases except in the case of thymine (T), for which RNA substitutes uracil (U). Under the genetic code, these RNA strands specify the sequence of amino acids within proteins in a process called translation.

Within eukaryotic cells, DNA is organized into long structures called chromosomes. Before typical cell division, these chromosomes are duplicated in the process of DNA replication, providing a complete set of chromosomes for each daughter cell. Eukaryotic organisms (animals, plants, fungi and protists) store most of their DNA inside the cell nucleus as nuclear DNA, and some in the mitochondria as mitochondrial DNA or in chloroplasts as chloroplast DNA. In contrast, prokaryotes (bacteria and archaea) store their DNA only in the cytoplasm, in circular chromosomes. Within eukaryotic chromosomes, chromatin proteins, such as histones, compact and organize DNA. These compacting structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed.

Properties

Chemical structure of DNA; hydrogen bonds shown as dotted lines. Each end of the double helix has an exposed 5' phosphate on one strand and an exposed 3′ hydroxyl group (—OH) on the other.

DNA is a long polymer made from repeating units called nucleotides. The structure of DNA is dynamic along its length, being capable of coiling into tight loops and other shapes. In all species it is composed of two helical chains, bound to each other by hydrogen bonds. Both chains are coiled around the same axis, and have the same pitch of 34 ångströms (3.4 nm). The pair of chains have a radius of 10 Å (1.0 nm). According to another study, when measured in a different solution, the DNA chain measured 22–26 Å (2.2–2.6 nm) wide, and one nucleotide unit measured 3.3 Å (0.33 nm) long. The buoyant density of most DNA is 1.7g/cm.

DNA does not usually exist as a single strand, but instead as a pair of strands that are held tightly together. These two long strands coil around each other, in the shape of a double helix. The nucleotide contains both a segment of the backbone of the molecule (which holds the chain together) and a nucleobase (which interacts with the other DNA strand in the helix). A nucleobase linked to a sugar is called a nucleoside, and a base linked to a sugar and to one or more phosphate groups is called a nucleotide. A biopolymer comprising multiple linked nucleotides (as in DNA) is called a polynucleotide.

The backbone of the DNA strand is made from alternating phosphate and sugar groups. The sugar in DNA is 2-deoxyribose, which is a pentose (five-carbon) sugar. The sugars are joined by phosphate groups that form phosphodiester bonds between the third and fifth carbon atoms of adjacent sugar rings. These are known as the 3′-end (three prime end), and 5′-end (five prime end) carbons, the prime symbol being used to distinguish these carbon atoms from those of the base to which the deoxyribose forms a glycosidic bond.

Therefore, any DNA strand normally has one end at which there is a phosphate group attached to the 5′ carbon of a ribose (the 5′ phosphoryl) and another end at which there is a free hydroxyl group attached to the 3′ carbon of a ribose (the 3′ hydroxyl). The orientation of the 3′ and 5′ carbons along the sugar-phosphate backbone confers directionality (sometimes called polarity) to each DNA strand. In a nucleic acid double helix, the direction of the nucleotides in one strand is opposite to their direction in the other strand: the strands are antiparallel. The asymmetric ends of DNA strands are said to have a directionality of five prime end (5′ ), and three prime end (3′), with the 5′ end having a terminal phosphate group and the 3′ end a terminal hydroxyl group. One major difference between DNA and RNA is the sugar, with the 2-deoxyribose in DNA being replaced by the related pentose sugar ribose in RNA.

A section of DNA. The bases lie horizontally between the two spiraling strands (animated version).

The DNA double helix is stabilized primarily by two forces: hydrogen bonds between nucleotides and base-stacking interactions among aromatic nucleobases. The four bases found in DNA are adenine (A), cytosine (C), guanine (G) and thymine (T). These four bases are attached to the sugar-phosphate to form the complete nucleotide, as shown for adenosine monophosphate. Adenine pairs with thymine and guanine pairs with cytosine, forming A-T and G-C base pairs.

Nucleobase classification

The nucleobases are classified into two types: the purines, A and G, which are fused five- and six-membered heterocyclic compounds, and the pyrimidines, the six-membered rings C and T. A fifth pyrimidine nucleobase, uracil (U), usually takes the place of thymine in RNA and differs from thymine by lacking a methyl group on its ring. In addition to RNA and DNA, many artificial nucleic acid analogues have been created to study the properties of nucleic acids, or for use in biotechnology.

Non-canonical bases

Modified bases occur in DNA. The first of these recognized was 5-methylcytosine, which was found in the genome of Mycobacterium tuberculosis in 1925. The reason for the presence of these noncanonical bases in bacterial viruses (bacteriophages) is to avoid the restriction enzymes present in bacteria. This enzyme system acts at least in part as a molecular immune system protecting bacteria from infection by viruses. Modifications of the bases cytosine and adenine, the more common and modified DNA bases, play vital roles in the epigenetic control of gene expression in plants and animals.

A number of noncanonical bases are known to occur in DNA. Most of these are modifications of the canonical bases plus uracil.

  • Modified Adenine
    • N6-carbamoyl-methyladenine
    • N6-methyadenine
  • Modified Guanine
    • 7-Deazaguanine
    • 7-Methylguanine
  • Modified Cytosine
    • N4-Methylcytosine
    • 5-Carboxylcytosine
    • 5-Formylcytosine
    • 5-Glycosylhydroxymethylcytosine
    • 5-Hydroxycytosine
    • 5-Methylcytosine
  • Modified Thymidine
    • α-Glutamythymidine
    • α-Putrescinylthymine
  • Uracil and modifications
    • Base J
    • Uracil
    • 5-Dihydroxypentauracil
    • 5-Hydroxymethyldeoxyuracil
  • Others
    • Deoxyarchaeosine
    • 2,6-Diaminopurine (2-Aminoadenine)

Grooves

DNA major and minor grooves. The latter is a binding site for the Hoechst stain dye 33258.

Twin helical strands form the DNA backbone. Another double helix may be found tracing the spaces, or grooves, between the strands. These voids are adjacent to the base pairs and may provide a binding site. As the strands are not symmetrically located with respect to each other, the grooves are unequally sized. The major groove is 22 ångströms (2.2 nm) wide, while the minor groove is 12 Å (1.2 nm) in width. Due to the larger width of the major groove, the edges of the bases are more accessible in the major groove than in the minor groove. As a result, proteins such as transcription factors that can bind to specific sequences in double-stranded DNA usually make contact with the sides of the bases exposed in the major groove. This situation varies in unusual conformations of DNA within the cell (see below), but the major and minor grooves are always named to reflect the differences in width that would be seen if the DNA was twisted back into the ordinary B form.

Base pairing

Further information: Base pair
Top, a GC base pair with three hydrogen bonds. Bottom, an AT base pair with two hydrogen bonds. Non-covalent hydrogen bonds between the pairs are shown as dashed lines.

In a DNA double helix, each type of nucleobase on one strand bonds with just one type of nucleobase on the other strand. This is called complementary base pairing. Purines form hydrogen bonds to pyrimidines, with adenine bonding only to thymine in two hydrogen bonds, and cytosine bonding only to guanine in three hydrogen bonds. This arrangement of two nucleotides binding together across the double helix (from six-carbon ring to six-carbon ring) is called a Watson-Crick base pair. DNA with high GC-content is more stable than DNA with low GC-content. A Hoogsteen base pair (hydrogen bonding the 6-carbon ring to the 5-carbon ring) is a rare variation of base-pairing. As hydrogen bonds are not covalent, they can be broken and rejoined relatively easily. The two strands of DNA in a double helix can thus be pulled apart like a zipper, either by a mechanical force or high temperature. As a result of this base pair complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. This reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in organisms.

ssDNA vs. dsDNA

Most DNA molecules are actually two polymer strands, bound together in a helical fashion by noncovalent bonds; this double-stranded (dsDNA) structure is maintained largely by the intrastrand base stacking interactions, which are strongest for G,C stacks. The two strands can come apart—a process known as melting—to form two single-stranded DNA (ssDNA) molecules. Melting occurs at high temperatures, low salt and high pH (low pH also melts DNA, but since DNA is unstable due to acid depurination, low pH is rarely used).

The stability of the dsDNA form depends not only on the GC-content (% G,C basepairs) but also on sequence (since stacking is sequence specific) and also length (longer molecules are more stable). The stability can be measured in various ways; a common way is the melting temperature (also called Tm value), which is the temperature at which 50% of the double-strand molecules are converted to single-strand molecules; melting temperature is dependent on ionic strength and the concentration of DNA. As a result, it is both the percentage of GC base pairs and the overall length of a DNA double helix that determines the strength of the association between the two strands of DNA. Long DNA helices with a high GC-content have more strongly interacting strands, while short helices with high AT content have more weakly interacting strands. In biology, parts of the DNA double helix that need to separate easily, such as the TATAAT Pribnow box in some promoters, tend to have a high AT content, making the strands easier to pull apart.

In the laboratory, the strength of this interaction can be measured by finding the melting temperature Tm necessary to break half of the hydrogen bonds. When all the base pairs in a DNA double helix melt, the strands separate and exist in solution as two entirely independent molecules. These single-stranded DNA molecules have no single common shape, but some conformations are more stable than others.

Amount

Schematic karyogram of a human. It shows 22 homologous chromosomes, both the female (XX) and male (XY) versions of the sex chromosome (bottom right), as well as the mitochondrial genome (to scale at bottom left). The blue scale to the left of each chromosome pair (and the mitochondrial genome) shows its length in terms of millions of DNA base pairs.Further information: Karyotype

In humans, the total female diploid nuclear genome per cell extends for 6.37 Gigabase pairs (Gbp), is 208.23 cm long and weighs 6.51 picograms (pg). Male values are 6.27 Gbp, 205.00 cm, 6.41 pg. Each DNA polymer can contain hundreds of millions of nucleotides, such as in chromosome 1. Chromosome 1 is the largest human chromosome with approximately 220 million base pairs, and would be 85 mm long if straightened.

In eukaryotes, in addition to nuclear DNA, there is also mitochondrial DNA (mtDNA) which encodes certain proteins used by the mitochondria. The mtDNA is usually relatively small in comparison to the nuclear DNA. For example, the human mitochondrial DNA forms closed circular molecules, each of which contains 16,569 DNA base pairs, with each such molecule normally containing a full set of the mitochondrial genes. Each human mitochondrion contains, on average, approximately 5 such mtDNA molecules. Each human cell contains approximately 100 mitochondria, giving a total number of mtDNA molecules per human cell of approximately 500. However, the amount of mitochondria per cell also varies by cell type, and an egg cell can contain 100,000 mitochondria, corresponding to up to 1,500,000 copies of the mitochondrial genome (constituting up to 90% of the DNA of the cell).

Sense and antisense

Further information: Sense (molecular biology)

A DNA sequence is called a "sense" sequence if it is the same as that of a messenger RNA copy that is translated into protein. The sequence on the opposite strand is called the "antisense" sequence. Both sense and antisense sequences can exist on different parts of the same strand of DNA (i.e. both strands can contain both sense and antisense sequences). In both prokaryotes and eukaryotes, antisense RNA sequences are produced, but the functions of these RNAs are not entirely clear. One proposal is that antisense RNAs are involved in regulating gene expression through RNA-RNA base pairing.

A few DNA sequences in prokaryotes and eukaryotes, and more in plasmids and viruses, blur the distinction between sense and antisense strands by having overlapping genes. In these cases, some DNA sequences do double duty, encoding one protein when read along one strand, and a second protein when read in the opposite direction along the other strand. In bacteria, this overlap may be involved in the regulation of gene transcription, while in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome.

Supercoiling

Further information: DNA supercoil

DNA can be twisted like a rope in a process called DNA supercoiling. With DNA in its "relaxed" state, a strand usually circles the axis of the double helix once every 10.4 base pairs, but if the DNA is twisted the strands become more tightly or more loosely wound. If the DNA is twisted in the direction of the helix, this is positive supercoiling, and the bases are held more tightly together. If they are twisted in the opposite direction, this is negative supercoiling, and the bases come apart more easily. In nature, most DNA has slight negative supercoiling that is introduced by enzymes called topoisomerases. These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as transcription and DNA replication.

Alternative DNA structures

Further information: Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid, Molecular models of DNA, and DNA structure
From left to right, the structures of A, B and Z-DNA

DNA exists in many possible conformations that include A-DNA, B-DNA, and Z-DNA forms, although only B-DNA and Z-DNA have been directly observed in functional organisms. The conformation that DNA adopts depends on the hydration level, DNA sequence, the amount and direction of supercoiling, chemical modifications of the bases, the type and concentration of metal ions, and the presence of polyamines in solution.

The first published reports of A-DNA X-ray diffraction patterns—and also B-DNA—used analyses based on Patterson functions that provided only a limited amount of structural information for oriented fibers of DNA. An alternative analysis was proposed by Wilkins et al. in 1953 for the in vivo B-DNA X-ray diffraction-scattering patterns of highly hydrated DNA fibers in terms of squares of Bessel functions. In the same journal, James Watson and Francis Crick presented their molecular modeling analysis of the DNA X-ray diffraction patterns to suggest that the structure was a double helix.

Although the B-DNA form is most common under the conditions found in cells, it is not a well-defined conformation but a family of related DNA conformations that occur at the high hydration levels present in cells. Their corresponding X-ray diffraction and scattering patterns are characteristic of molecular paracrystals with a significant degree of disorder.

Compared to B-DNA, the A-DNA form is a wider right-handed spiral, with a shallow, wide minor groove and a narrower, deeper major groove. The A form occurs under non-physiological conditions in partly dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands, and in enzyme-DNA complexes. Segments of DNA where the bases have been chemically modified by methylation may undergo a larger change in conformation and adopt the Z form. Here, the strands turn about the helical axis in a left-handed spiral, the opposite of the more common B form. These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in the regulation of transcription.

Alternative DNA chemistry

Further information: hypothetical types of biochemistry

For many years, exobiologists have proposed the existence of a shadow biosphere, a postulated microbial biosphere of Earth that uses radically different biochemical and molecular processes than currently known life. One of the proposals was the existence of lifeforms that use arsenic instead of phosphorus in DNA. A report in 2010 of the possibility in the bacterium GFAJ-1 was announced, though the research was disputed, and evidence suggests the bacterium actively prevents the incorporation of arsenic into the DNA backbone and other biomolecules.

Quadruplex structures

Further information: G-quadruplex
DNA quadruplex formed by telomere repeats. The looped conformation of the DNA backbone is very different from the typical DNA helix. The green spheres in the center represent potassium ions.

At the ends of the linear chromosomes are specialized regions of DNA called telomeres. The main function of these regions is to allow the cell to replicate chromosome ends using the enzyme telomerase, as the enzymes that normally replicate DNA cannot copy the extreme 3′ ends of chromosomes. These specialized chromosome caps also help protect the DNA ends, and stop the DNA repair systems in the cell from treating them as damage to be corrected. In human cells, telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence.

These guanine-rich sequences may stabilize chromosome ends by forming structures of stacked sets of four-base units, rather than the usual base pairs found in other DNA molecules. Here, four guanine bases, known as a guanine tetrad, form a flat plate. These flat four-base units then stack on top of each other to form a stable G-quadruplex structure. These structures are stabilized by hydrogen bonding between the edges of the bases and chelation of a metal ion in the centre of each four-base unit. Other structures can also be formed, with the central set of four bases coming from either a single strand folded around the bases, or several different parallel strands, each contributing one base to the central structure.

In addition to these stacked structures, telomeres also form large loop structures called telomere loops, or T-loops. Here, the single-stranded DNA curls around in a long circle stabilized by telomere-binding proteins. At the very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere strand disrupting the double-helical DNA and base pairing to one of the two strands. This triple-stranded structure is called a displacement loop or D-loop.

Branched DNA

Further information: Branched DNA and DNA nanotechnology
Single branch Multiple branches
Branched DNA can form networks containing multiple branches.

In DNA, fraying occurs when non-complementary regions exist at the end of an otherwise complementary double-strand of DNA. However, branched DNA can occur if a third strand of DNA is introduced and contains adjoining regions able to hybridize with the frayed regions of the pre-existing double-strand. Although the simplest example of branched DNA involves only three strands of DNA, complexes involving additional strands and multiple branches are also possible. Branched DNA can be used in nanotechnology to construct geometric shapes, see the section on uses in technology below.

Artificial bases

Main article: Nucleic acid analogue

Several artificial nucleobases have been synthesized, and successfully incorporated in the eight-base DNA analogue named Hachimoji DNA. Dubbed S, B, P, and Z, these artificial bases are capable of bonding with each other in a predictable way (S–B and P–Z), maintain the double helix structure of DNA, and be transcribed to RNA. Their existence could be seen as an indication that there is nothing special about the four natural nucleobases that evolved on Earth. On the other hand, DNA is tightly related to RNA which does not only act as a transcript of DNA but also performs as molecular machines many tasks in cells. For this purpose it has to fold into a structure. It has been shown that to allow to create all possible structures at least four bases are required for the corresponding RNA, while a higher number is also possible but this would be against the natural principle of least effort.

Acidity

The phosphate groups of DNA give it similar acidic properties to phosphoric acid and it can be considered as a strong acid. It will be fully ionized at a normal cellular pH, releasing protons which leave behind negative charges on the phosphate groups. These negative charges protect DNA from breakdown by hydrolysis by repelling nucleophiles which could hydrolyze it.

Macroscopic appearance

Impure DNA extracted from an orange

Pure DNA extracted from cells forms white, stringy clumps.

Chemical modifications and altered DNA packaging

Base modifications and DNA packaging

Further information: DNA methylation and Chromatin remodeling
cytosine 5-methylcytosine thymine
Structure of cytosine with and without the 5-methyl group. Deamination converts 5-methylcytosine into thymine.

The expression of genes is influenced by how the DNA is packaged in chromosomes, in a structure called chromatin. Base modifications can be involved in packaging, with regions that have low or no gene expression usually containing high levels of methylation of cytosine bases. DNA packaging and its influence on gene expression can also occur by covalent modifications of the histone protein core around which DNA is wrapped in the chromatin structure or else by remodeling carried out by chromatin remodeling complexes (see Chromatin remodeling). There is, further, crosstalk between DNA methylation and histone modification, so they can coordinately affect chromatin and gene expression.

For one example, cytosine methylation produces 5-methylcytosine, which is important for X-inactivation of chromosomes. The average level of methylation varies between organisms—the worm Caenorhabditis elegans lacks cytosine methylation, while vertebrates have higher levels, with up to 1% of their DNA containing 5-methylcytosine. Despite the importance of 5-methylcytosine, it can deaminate to leave a thymine base, so methylated cytosines are particularly prone to mutations. Other base modifications include adenine methylation in bacteria, the presence of 5-hydroxymethylcytosine in the brain, and the glycosylation of uracil to produce the "J-base" in kinetoplastids.

Damage

Further information: DNA damage (naturally occurring), Mutation, and DNA damage theory of aging
A covalent adduct between a metabolically activated form of benzopyrene, the major mutagen in tobacco smoke, and DNA

DNA can be damaged by many sorts of mutagens, which change the DNA sequence. Mutagens include oxidizing agents, alkylating agents and also high-energy electromagnetic radiation such as ultraviolet light and X-rays. The type of DNA damage produced depends on the type of mutagen. For example, UV light can damage DNA by producing thymine dimers, which are cross-links between pyrimidine bases. On the other hand, oxidants such as free radicals or hydrogen peroxide produce multiple forms of damage, including base modifications, particularly of guanosine, and double-strand breaks. A typical human cell contains about 150,000 bases that have suffered oxidative damage. Of these oxidative lesions, the most dangerous are double-strand breaks, as these are difficult to repair and can produce point mutations, insertions, deletions from the DNA sequence, and chromosomal translocations. These mutations can cause cancer. Because of inherent limits in the DNA repair mechanisms, if humans lived long enough, they would all eventually develop cancer. DNA damages that are naturally occurring, due to normal cellular processes that produce reactive oxygen species, the hydrolytic activities of cellular water, etc., also occur frequently. Although most of these damages are repaired, in any cell some DNA damage may remain despite the action of repair processes. These remaining DNA damages accumulate with age in mammalian postmitotic tissues. This accumulation appears to be an important underlying cause of aging.

Many mutagens fit into the space between two adjacent base pairs, this is called intercalation. Most intercalators are aromatic and planar molecules; examples include ethidium bromide, acridines, daunomycin, and doxorubicin. For an intercalator to fit between base pairs, the bases must separate, distorting the DNA strands by unwinding of the double helix. This inhibits both transcription and DNA replication, causing toxicity and mutations. As a result, DNA intercalators may be carcinogens, and in the case of thalidomide, a teratogen. Others such as benzopyrene diol epoxide and aflatoxin form DNA adducts that induce errors in replication. Nevertheless, due to their ability to inhibit DNA transcription and replication, other similar toxins are also used in chemotherapy to inhibit rapidly growing cancer cells.

Biological functions

Location of eukaryote nuclear DNA within the chromosomes

DNA usually occurs as linear chromosomes in eukaryotes, and circular chromosomes in prokaryotes. The set of chromosomes in a cell makes up its genome; the human genome has approximately 3 billion base pairs of DNA arranged into 46 chromosomes. The information carried by DNA is held in the sequence of pieces of DNA called genes. Transmission of genetic information in genes is achieved via complementary base pairing. For example, in transcription, when a cell uses the information in a gene, the DNA sequence is copied into a complementary RNA sequence through the attraction between the DNA and the correct RNA nucleotides. Usually, this RNA copy is then used to make a matching protein sequence in a process called translation, which depends on the same interaction between RNA nucleotides. In an alternative fashion, a cell may copy its genetic information in a process called DNA replication. The details of these functions are covered in other articles; here the focus is on the interactions between DNA and other molecules that mediate the function of the genome.

Genes and genomes

Further information: Cell nucleus, Chromatin, Chromosome, Gene, and Noncoding DNA

Genomic DNA is tightly and orderly packed in the process called DNA condensation, to fit the small available volumes of the cell. In eukaryotes, DNA is located in the cell nucleus, with small amounts in mitochondria and chloroplasts. In prokaryotes, the DNA is held within an irregularly shaped body in the cytoplasm called the nucleoid. The genetic information in a genome is held within genes, and the complete set of this information in an organism is called its genotype. A gene is a unit of heredity and is a region of DNA that influences a particular characteristic in an organism. Genes contain an open reading frame that can be transcribed, and regulatory sequences such as promoters and enhancers, which control transcription of the open reading frame.

In many species, only a small fraction of the total sequence of the genome encodes protein. For example, only about 1.5% of the human genome consists of protein-coding exons, with over 50% of human DNA consisting of non-coding repetitive sequences. The reasons for the presence of so much noncoding DNA in eukaryotic genomes and the extraordinary differences in genome size, or C-value, among species, represent a long-standing puzzle known as the "C-value enigma". However, some DNA sequences that do not code protein may still encode functional non-coding RNA molecules, which are involved in the regulation of gene expression.

T7 RNA polymerase (blue) producing an mRNA (green) from a DNA template (orange)

Some noncoding DNA sequences play structural roles in chromosomes. Telomeres and centromeres typically contain few genes but are important for the function and stability of chromosomes. An abundant form of noncoding DNA in humans are pseudogenes, which are copies of genes that have been disabled by mutation. These sequences are usually just molecular fossils, although they can occasionally serve as raw genetic material for the creation of new genes through the process of gene duplication and divergence.

Transcription and translation

Further information: Genetic code, Transcription (genetics), and Protein biosynthesis

A gene is a sequence of DNA that contains genetic information and can influence the phenotype of an organism. Within a gene, the sequence of bases along a DNA strand defines a messenger RNA sequence, which then defines one or more protein sequences. The relationship between the nucleotide sequences of genes and the amino-acid sequences of proteins is determined by the rules of translation, known collectively as the genetic code. The genetic code consists of three-letter 'words' called codons formed from a sequence of three nucleotides (e.g. ACT, CAG, TTT).

In transcription, the codons of a gene are copied into messenger RNA by RNA polymerase. This RNA copy is then decoded by a ribosome that reads the RNA sequence by base-pairing the messenger RNA to transfer RNA, which carries amino acids. Since there are 4 bases in 3-letter combinations, there are 64 possible codons (4 combinations). These encode the twenty standard amino acids, giving most amino acids more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region; these are the TAG, TAA, and TGA codons, (UAG, UAA, and UGA on the mRNA).

Replication

Further information: DNA replication
DNA replication: The double helix is unwound by a helicase and topo­iso­merase. Next, one DNA polymerase produces the leading strand copy. Another DNA polymerase binds to the lagging strand. This enzyme makes discontinuous segments (called Okazaki fragments) before DNA ligase joins them together.

Cell division is essential for an organism to grow, but, when a cell divides, it must replicate the DNA in its genome so that the two daughter cells have the same genetic information as their parent. The double-stranded structure of DNA provides a simple mechanism for DNA replication. Here, the two strands are separated and then each strand's complementary DNA sequence is recreated by an enzyme called DNA polymerase. This enzyme makes the complementary strand by finding the correct base through complementary base pairing and bonding it onto the original strand. As DNA polymerases can only extend a DNA strand in a 5′ to 3′ direction, different mechanisms are used to copy the antiparallel strands of the double helix. In this way, the base on the old strand dictates which base appears on the new strand, and the cell ends up with a perfect copy of its DNA.

Extracellular nucleic acids

Naked extracellular DNA (eDNA), most of it released by cell death, is nearly ubiquitous in the environment. Its concentration in soil may be as high as 2 μg/L, and its concentration in natural aquatic environments may be as high at 88 μg/L. Various possible functions have been proposed for eDNA: it may be involved in horizontal gene transfer; it may provide nutrients; and it may act as a buffer to recruit or titrate ions or antibiotics. Extracellular DNA acts as a functional extracellular matrix component in the biofilms of several bacterial species. It may act as a recognition factor to regulate the attachment and dispersal of specific cell types in the biofilm; it may contribute to biofilm formation; and it may contribute to the biofilm's physical strength and resistance to biological stress.

Cell-free fetal DNA is found in the blood of the mother, and can be sequenced to determine a great deal of information about the developing fetus.

Under the name of environmental DNA eDNA has seen increased use in the natural sciences as a survey tool for ecology, monitoring the movements and presence of species in water, air, or on land, and assessing an area's biodiversity.

Neutrophil extracellular traps

Main article: Neutrophil extracellular traps

Neutrophil extracellular traps (NETs) are networks of extracellular fibers, primarily composed of DNA, which allow neutrophils, a type of white blood cell, to kill extracellular pathogens while minimizing damage to the host cells.

Interactions with proteins

All the functions of DNA depend on interactions with proteins. These protein interactions can be non-specific, or the protein can bind specifically to a single DNA sequence. Enzymes can also bind to DNA and of these, the polymerases that copy the DNA base sequence in transcription and DNA replication are particularly important.

DNA-binding proteins

Further information: DNA-binding protein
Interaction of DNA (in orange) with histones (in blue). These proteins' basic amino acids bind to the acidic phosphate groups on DNA.

Structural proteins that bind DNA are well-understood examples of non-specific DNA-protein interactions. Within chromosomes, DNA is held in complexes with structural proteins. These proteins organize the DNA into a compact structure called chromatin. In eukaryotes, this structure involves DNA binding to a complex of small basic proteins called histones, while in prokaryotes multiple types of proteins are involved. The histones form a disk-shaped complex called a nucleosome, which contains two complete turns of double-stranded DNA wrapped around its surface. These non-specific interactions are formed through basic residues in the histones, making ionic bonds to the acidic sugar-phosphate backbone of the DNA, and are thus largely independent of the base sequence. Chemical modifications of these basic amino acid residues include methylation, phosphorylation, and acetylation. These chemical changes alter the strength of the interaction between the DNA and the histones, making the DNA more or less accessible to transcription factors and changing the rate of transcription. Other non-specific DNA-binding proteins in chromatin include the high-mobility group proteins, which bind to bent or distorted DNA. These proteins are important in bending arrays of nucleosomes and arranging them into the larger structures that make up chromosomes.

A distinct group of DNA-binding proteins is the DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication protein A is the best-understood member of this family and is used in processes where the double helix is separated, including DNA replication, recombination, and DNA repair. These binding proteins seem to stabilize single-stranded DNA and protect it from forming stem-loops or being degraded by nucleases.

The lambda repressor helix-turn-helix transcription factor bound to its DNA target

In contrast, other proteins have evolved to bind to particular DNA sequences. The most intensively studied of these are the various transcription factors, which are proteins that regulate transcription. Each transcription factor binds to one particular set of DNA sequences and activates or inhibits the transcription of genes that have these sequences close to their promoters. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins; this locates the polymerase at the promoter and allows it to begin transcription. Alternatively, transcription factors can bind enzymes that modify the histones at the promoter. This changes the accessibility of the DNA template to the polymerase.

As these DNA targets can occur throughout an organism's genome, changes in the activity of one type of transcription factor can affect thousands of genes. Consequently, these proteins are often the targets of the signal transduction processes that control responses to environmental changes or cellular differentiation and development. The specificity of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of the DNA bases, allowing them to "read" the DNA sequence. Most of these base-interactions are made in the major groove, where the bases are most accessible.

DNA-modifying enzymes

Nucleases and ligases

The restriction enzyme EcoRV (green) in a complex with its substrate DNA

Nucleases are enzymes that cut DNA strands by catalyzing the hydrolysis of the phosphodiester bonds. Nucleases that hydrolyse nucleotides from the ends of DNA strands are called exonucleases, while endonucleases cut within strands. The most frequently used nucleases in molecular biology are the restriction endonucleases, which cut DNA at specific sequences. For instance, the EcoRV enzyme shown to the left recognizes the 6-base sequence 5′-GATATC-3′ and makes a cut at the horizontal line. In nature, these enzymes protect bacteria against phage infection by digesting the phage DNA when it enters the bacterial cell, acting as part of the restriction modification system. In technology, these sequence-specific nucleases are used in molecular cloning and DNA fingerprinting.

Enzymes called DNA ligases can rejoin cut or broken DNA strands. Ligases are particularly important in lagging strand DNA replication, as they join the short segments of DNA produced at the replication fork into a complete copy of the DNA template. They are also used in DNA repair and genetic recombination.

Topoisomerases and helicases

Topoisomerases are enzymes with both nuclease and ligase activity. These proteins change the amount of supercoiling in DNA. Some of these enzymes work by cutting the DNA helix and allowing one section to rotate, thereby reducing its level of supercoiling; the enzyme then seals the DNA break. Other types of these enzymes are capable of cutting one DNA helix and then passing a second strand of DNA through this break, before rejoining the helix. Topoisomerases are required for many processes involving DNA, such as DNA replication and transcription.

Helicases are proteins that are a type of molecular motor. They use the chemical energy in nucleoside triphosphates, predominantly adenosine triphosphate (ATP), to break hydrogen bonds between bases and unwind the DNA double helix into single strands. These enzymes are essential for most processes where enzymes need to access the DNA bases.

Polymerases

Polymerases are enzymes that synthesize polynucleotide chains from nucleoside triphosphates. The sequence of their products is created based on existing polynucleotide chains—which are called templates. These enzymes function by repeatedly adding a nucleotide to the 3′ hydroxyl group at the end of the growing polynucleotide chain. As a consequence, all polymerases work in a 5′ to 3′ direction. In the active site of these enzymes, the incoming nucleoside triphosphate base-pairs to the template: this allows polymerases to accurately synthesize the complementary strand of their template. Polymerases are classified according to the type of template that they use.

In DNA replication, DNA-dependent DNA polymerases make copies of DNA polynucleotide chains. To preserve biological information, it is essential that the sequence of bases in each copy are precisely complementary to the sequence of bases in the template strand. Many DNA polymerases have a proofreading activity. Here, the polymerase recognizes the occasional mistakes in the synthesis reaction by the lack of base pairing between the mismatched nucleotides. If a mismatch is detected, a 3′ to 5′ exonuclease activity is activated and the incorrect base removed. In most organisms, DNA polymerases function in a large complex called the replisome that contains multiple accessory subunits, such as the DNA clamp or helicases.

RNA-dependent DNA polymerases are a specialized class of polymerases that copy the sequence of an RNA strand into DNA. They include reverse transcriptase, which is a viral enzyme involved in the infection of cells by retroviruses, and telomerase, which is required for the replication of telomeres. For example, HIV reverse transcriptase is an enzyme for AIDS virus replication. Telomerase is an unusual polymerase because it contains its own RNA template as part of its structure. It synthesizes telomeres at the ends of chromosomes. Telomeres prevent fusion of the ends of neighboring chromosomes and protect chromosome ends from damage.

Transcription is carried out by a DNA-dependent RNA polymerase that copies the sequence of a DNA strand into RNA. To begin transcribing a gene, the RNA polymerase binds to a sequence of DNA called a promoter and separates the DNA strands. It then copies the gene sequence into a messenger RNA transcript until it reaches a region of DNA called the terminator, where it halts and detaches from the DNA. As with human DNA-dependent DNA polymerases, RNA polymerase II, the enzyme that transcribes most of the genes in the human genome, operates as part of a large protein complex with multiple regulatory and accessory subunits.

Genetic recombination

Further information: Genetic recombination
Structure of the Holliday junction intermediate in genetic recombination. The four separate DNA strands are coloured red, blue, green and yellow.
A current model of meiotic recombination, initiated by a double-strand break or gap, followed by pairing with an homologous chromosome and strand invasion to initiate the recombinational repair process. Repair of the gap can lead to crossover (CO) or non-crossover (NCO) of the flanking regions. CO recombination is thought to occur by the Double Holliday Junction (DHJ) model, illustrated on the right, above. NCO recombinants are thought to occur primarily by the Synthesis Dependent Strand Annealing (SDSA) model, illustrated on the left, above. Most recombination events appear to be the SDSA type.

A DNA helix usually does not interact with other segments of DNA, and in human cells, the different chromosomes even occupy separate areas in the nucleus called "chromosome territories". This physical separation of different chromosomes is important for the ability of DNA to function as a stable repository for information, as one of the few times chromosomes interact is in chromosomal crossover which occurs during sexual reproduction, when genetic recombination occurs. Chromosomal crossover is when two DNA helices break, swap a section and then rejoin.

Recombination allows chromosomes to exchange genetic information and produces new combinations of genes, which increases the efficiency of natural selection and can be important in the rapid evolution of new proteins. Genetic recombination can also be involved in DNA repair, particularly in the cell's response to double-strand breaks.

The most common form of chromosomal crossover is homologous recombination, where the two chromosomes involved share very similar sequences. Non-homologous recombination can be damaging to cells, as it can produce chromosomal translocations and genetic abnormalities. The recombination reaction is catalyzed by enzymes known as recombinases, such as RAD51. The first step in recombination is a double-stranded break caused by either an endonuclease or damage to the DNA. A series of steps catalyzed in part by the recombinase then leads to joining of the two helices by at least one Holliday junction, in which a segment of a single strand in each helix is annealed to the complementary strand in the other helix. The Holliday junction is a tetrahedral junction structure that can be moved along the pair of chromosomes, swapping one strand for another. The recombination reaction is then halted by cleavage of the junction and re-ligation of the released DNA. Only strands of like polarity exchange DNA during recombination. There are two types of cleavage: east-west cleavage and north–south cleavage. The north–south cleavage nicks both strands of DNA, while the east–west cleavage has one strand of DNA intact. The formation of a Holliday junction during recombination makes it possible for genetic diversity, genes to exchange on chromosomes, and expression of wild-type viral genomes.

Evolution

Further information: RNA world hypothesis

DNA contains the genetic information that allows all forms of life to function, grow and reproduce. However, it is unclear how long in the 4-billion-year history of life DNA has performed this function, as it has been proposed that the earliest forms of life may have used RNA as their genetic material. RNA may have acted as the central part of early cell metabolism as it can both transmit genetic information and carry out catalysis as part of ribozymes. This ancient RNA world where nucleic acid would have been used for both catalysis and genetics may have influenced the evolution of the current genetic code based on four nucleotide bases. This would occur, since the number of different bases in such an organism is a trade-off between a small number of bases increasing replication accuracy and a large number of bases increasing the catalytic efficiency of ribozymes. However, there is no direct evidence of ancient genetic systems, as recovery of DNA from most fossils is impossible because DNA survives in the environment for less than one million years, and slowly degrades into short fragments in solution. Claims for older DNA have been made, most notably a report of the isolation of a viable bacterium from a salt crystal 250 million years old, but these claims are controversial.

Building blocks of DNA (adenine, guanine, and related organic molecules) may have been formed extraterrestrially in outer space. Complex DNA and RNA organic compounds of life, including uracil, cytosine, and thymine, have also been formed in the laboratory under conditions mimicking those found in outer space, using starting chemicals, such as pyrimidine, found in meteorites. Pyrimidine, like polycyclic aromatic hydrocarbons (PAHs), the most carbon-rich chemical found in the universe, may have been formed in red giants or in interstellar cosmic dust and gas clouds.

Ancient DNA has been recovered from ancient organisms at a timescale where genome evolution can be directly observed, including from extinct organisms up to millions of years old, such as the woolly mammoth.

Uses in technology

Genetic engineering

Further information: Molecular biology, Nucleic acid methods, and Genetic engineering

Methods have been developed to purify DNA from organisms, such as phenol-chloroform extraction, and to manipulate it in the laboratory, such as restriction digests and the polymerase chain reaction. Modern biology and biochemistry make intensive use of these techniques in recombinant DNA technology. Recombinant DNA is a man-made DNA sequence that has been assembled from other DNA sequences. They can be transformed into organisms in the form of plasmids or in the appropriate format, by using a viral vector. The genetically modified organisms produced can be used to produce products such as recombinant proteins, used in medical research, or be grown in agriculture.

DNA profiling

Further information: DNA profiling

Forensic scientists can use DNA in blood, semen, skin, saliva or hair found at a crime scene to identify a matching DNA of an individual, such as a perpetrator. This process is formally termed DNA profiling, also called DNA fingerprinting. In DNA profiling, the lengths of variable sections of repetitive DNA, such as short tandem repeats and minisatellites, are compared between people. This method is usually an extremely reliable technique for identifying a matching DNA. However, identification can be complicated if the scene is contaminated with DNA from several people. DNA profiling was developed in 1984 by British geneticist Sir Alec Jeffreys, and first used in forensic science to convict Colin Pitchfork in the 1988 Enderby murders case.

The development of forensic science and the ability to now obtain genetic matching on minute samples of blood, skin, saliva, or hair has led to re-examining many cases. Evidence can now be uncovered that was scientifically impossible at the time of the original examination. Combined with the removal of the double jeopardy law in some places, this can allow cases to be reopened where prior trials have failed to produce sufficient evidence to convince a jury. People charged with serious crimes may be required to provide a sample of DNA for matching purposes. The most obvious defense to DNA matches obtained forensically is to claim that cross-contamination of evidence has occurred. This has resulted in meticulous strict handling procedures with new cases of serious crime.

DNA profiling is also used successfully to positively identify victims of mass casualty incidents, bodies or body parts in serious accidents, and individual victims in mass war graves, via matching to family members.

DNA profiling is also used in DNA paternity testing to determine if someone is the biological parent or grandparent of a child with the probability of parentage is typically 99.99% when the alleged parent is biologically related to the child. Normal DNA sequencing methods happen after birth, but there are new methods to test paternity while a mother is still pregnant.

DNA enzymes or catalytic DNA

Further information: Deoxyribozyme

Deoxyribozymes, also called DNAzymes or catalytic DNA, were first discovered in 1994. They are mostly single stranded DNA sequences isolated from a large pool of random DNA sequences through a combinatorial approach called in vitro selection or systematic evolution of ligands by exponential enrichment (SELEX). DNAzymes catalyze variety of chemical reactions including RNA-DNA cleavage, RNA-DNA ligation, amino acids phosphorylation-dephosphorylation, carbon-carbon bond formation, etc. DNAzymes can enhance catalytic rate of chemical reactions up to 100,000,000,000-fold over the uncatalyzed reaction. The most extensively studied class of DNAzymes is RNA-cleaving types which have been used to detect different metal ions and designing therapeutic agents. Several metal-specific DNAzymes have been reported including the GR-5 DNAzyme (lead-specific), the CA1-3 DNAzymes (copper-specific), the 39E DNAzyme (uranyl-specific) and the NaA43 DNAzyme (sodium-specific). The NaA43 DNAzyme, which is reported to be more than 10,000-fold selective for sodium over other metal ions, was used to make a real-time sodium sensor in cells.

Bioinformatics

Further information: Bioinformatics

Bioinformatics involves the development of techniques to store, data mine, search and manipulate biological data, including DNA nucleic acid sequence data. These have led to widely applied advances in computer science, especially string searching algorithms, machine learning, and database theory. String searching or matching algorithms, which find an occurrence of a sequence of letters inside a larger sequence of letters, were developed to search for specific sequences of nucleotides. The DNA sequence may be aligned with other DNA sequences to identify homologous sequences and locate the specific mutations that make them distinct. These techniques, especially multiple sequence alignment, are used in studying phylogenetic relationships and protein function. Data sets representing entire genomes' worth of DNA sequences, such as those produced by the Human Genome Project, are difficult to use without the annotations that identify the locations of genes and regulatory elements on each chromosome. Regions of DNA sequence that have the characteristic patterns associated with protein- or RNA-coding genes can be identified by gene finding algorithms, which allow researchers to predict the presence of particular gene products and their possible functions in an organism even before they have been isolated experimentally. Entire genomes may also be compared, which can shed light on the evolutionary history of particular organism and permit the examination of complex evolutionary events.

DNA nanotechnology

Further information: DNA nanotechnology
The DNA structure at left (schematic shown) will self-assemble into the structure visualized by atomic force microscopy at right. DNA nanotechnology is the field that seeks to design nanoscale structures using the molecular recognition properties of DNA molecules.

DNA nanotechnology uses the unique molecular recognition properties of DNA and other nucleic acids to create self-assembling branched DNA complexes with useful properties. DNA is thus used as a structural material rather than as a carrier of biological information. This has led to the creation of two-dimensional periodic lattices (both tile-based and using the DNA origami method) and three-dimensional structures in the shapes of polyhedra. Nanomechanical devices and algorithmic self-assembly have also been demonstrated, and these DNA structures have been used to template the arrangement of other molecules such as gold nanoparticles and streptavidin proteins. DNA and other nucleic acids are the basis of aptamers, synthetic oligonucleotide ligands for specific target molecules used in a range of biotechnology and biomedical applications.

History and anthropology

Further information: Phylogenetics and Genetic genealogy

Because DNA collects mutations over time, which are then inherited, it contains historical information, and, by comparing DNA sequences, geneticists can infer the evolutionary history of organisms, their phylogeny. This field of phylogenetics is a powerful tool in evolutionary biology. If DNA sequences within a species are compared, population geneticists can learn the history of particular populations. This can be used in studies ranging from ecological genetics to anthropology.

Information storage

Main article: DNA digital data storage

DNA as a storage device for information has enormous potential since it has much higher storage density compared to electronic devices. However, high costs, slow read and write times (memory latency), and insufficient reliability has prevented its practical use.

History

Further information: History of molecular biology
Maclyn McCarty (left) shakes hands with Francis Crick and James Watson, co-originators of the double-helix model based on the X-ray diffraction data and insights of Rosalind Franklin and Raymond Gosling.

DNA was first isolated by the Swiss physician Friedrich Miescher who, in 1869, discovered a microscopic substance in the pus of discarded surgical bandages. As it resided in the nuclei of cells, he called it "nuclein". In 1878, Albrecht Kossel isolated the non-protein component of "nuclein", nucleic acid, and later isolated its five primary nucleobases.

In 1909, Phoebus Levene identified the base, sugar, and phosphate nucleotide unit of RNA (then named "yeast nucleic acid"). In 1929, Levene identified deoxyribose sugar in "thymus nucleic acid" (DNA). Levene suggested that DNA consisted of a string of four nucleotide units linked together through the phosphate groups ("tetranucleotide hypothesis"). Levene thought the chain was short and the bases repeated in a fixed order. In 1927, Nikolai Koltsov proposed that inherited traits would be inherited via a "giant hereditary molecule" made up of "two mirror strands that would replicate in a semi-conservative fashion using each strand as a template". In 1928, Frederick Griffith in his experiment discovered that traits of the "smooth" form of Pneumococcus could be transferred to the "rough" form of the same bacteria by mixing killed "smooth" bacteria with the live "rough" form. This system provided the first clear suggestion that DNA carries genetic information.

In 1933, while studying virgin sea urchin eggs, Jean Brachet suggested that DNA is found in the cell nucleus and that RNA is present exclusively in the cytoplasm. At the time, "yeast nucleic acid" (RNA) was thought to occur only in plants, while "thymus nucleic acid" (DNA) only in animals. The latter was thought to be a tetramer, with the function of buffering cellular pH.

In 1937, William Astbury produced the first X-ray diffraction patterns that showed that DNA had a regular structure.

In 1943, Oswald Avery, along with co-workers Colin MacLeod and Maclyn McCarty, identified DNA as the transforming principle, supporting Griffith's suggestion (Avery–MacLeod–McCarty experiment). Erwin Chargaff developed and published observations now known as Chargaff's rules, stating that in DNA from any species of any organism, the amount of guanine should be equal to cytosine and the amount of adenine should be equal to thymine.

A blue plaque outside The Eagle pub in Cambridge, England commemorating Crick and Watson

Late in 1951, Francis Crick started working with James Watson at the Cavendish Laboratory within the University of Cambridge. DNA's role in heredity was confirmed in 1952 when Alfred Hershey and Martha Chase in the Hershey–Chase experiment showed that DNA is the genetic material of the enterobacteria phage T2.

Photo 51, showing X-ray diffraction pattern of DNA

In May 1952, Raymond Gosling, a graduate student working under the supervision of Rosalind Franklin, took an X-ray diffraction image, labeled as "Photo 51", at high hydration levels of DNA. This photo was given to Watson and Crick by Maurice Wilkins and was critical to their obtaining the correct structure of DNA. Franklin told Crick and Watson that the backbones had to be on the outside. Before then, Linus Pauling, and Watson and Crick, had erroneous models with the chains inside and the bases pointing outwards. Franklin's identification of the space group for DNA crystals revealed to Crick that the two DNA strands were antiparallel. In February 1953, Linus Pauling and Robert Corey proposed a model for nucleic acids containing three intertwined chains, with the phosphates near the axis, and the bases on the outside. Watson and Crick completed their model, which is now accepted as the first correct model of the double helix of DNA. On 28 February 1953 Crick interrupted patrons' lunchtime at The Eagle pub in Cambridge, England to announce that he and Watson had "discovered the secret of life".

Pencil sketch of the DNA double helix by Francis Crick in 1953

The 25 April 1953 issue of the journal Nature published a series of five articles giving the Watson and Crick double-helix structure DNA and evidence supporting it. The structure was reported in a letter titled "MOLECULAR STRUCTURE OF NUCLEIC ACIDS A Structure for Deoxyribose Nucleic Acid", in which they said, "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material." This letter was followed by a letter from Franklin and Gosling, which was the first publication of their own X-ray diffraction data and of their original analysis method. Then followed a letter by Wilkins and two of his colleagues, which contained an analysis of in vivo B-DNA X-ray patterns, and which supported the presence in vivo of the Watson and Crick structure.

In April 2023, scientists, based on new evidence, concluded that Rosalind Franklin was a contributor and "equal player" in the discovery process of DNA, rather than otherwise, as may have been presented subsequently after the time of the discovery.

In 1962, after Franklin's death, Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine. Nobel Prizes are awarded only to living recipients. A debate continues about who should receive credit for the discovery.

In an influential presentation in 1957, Crick laid out the central dogma of molecular biology, which foretold the relationship between DNA, RNA, and proteins, and articulated the "adaptor hypothesis". Final confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 through the Meselson–Stahl experiment. Further work by Crick and co-workers showed that the genetic code was based on non-overlapping triplets of bases, called codons, allowing Har Gobind Khorana, Robert W. Holley, and Marshall Warren Nirenberg to decipher the genetic code. These findings represent the birth of molecular biology.

In 1986, DNA analysis was first used for criminal investigative purposes when police in the UK requested Alec Jeffreys of the University of Leicester to verify or disprove a suspect's rape-murder "confession". In this particular case, the suspect had confessed to two rape-murders, but had later retracted his confession. DNA testing at the university labs soon disproved the veracity of the suspect's original "confession", and the suspect was exonerated from the murder-rape charges.

See also

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