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Revision as of 18:45, 16 February 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{chembox}} taken from revid 443358017 of page 8-Oxo-2'-deoxyguanosine for the Chem/Drugbox validation project (updated: 'CASNo').		Latest revision as of 21:16, 13 April 2024 edit Josve05a (talk | contribs)Autopatrolled, Extended confirmed users, New page reviewers, Pending changes reviewers, Rollbackers153,282 editsm Reverted edit by Josve05a (talk) to last version by IztwozTag: Rollback
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	{{ambox | text = This page contains a copy of the infobox ({{tl|chembox}}) taken from revid of page ] with values updated to verified values.}}
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	|ImageSize=200px		| ImageSize=200px
	|IUPACName=2-amino-9--3,7-dihydropurine-6,8-dione		| IUPACName=2-amino-9--3,7-dihydropurine-6,8-dione
	|OtherNames=7,8-Dihydro-8-oxo-2'-deoxyguanosine; 7,8-Dihydro-8-oxodeoxyguanosine; 8-Hydroxy-2'-deoxyguanosine; 8-Hydroxydeoxyguanosine; 8-Oxo-2'-deoxyguanosine; 8-Oxo-7,8-dihydro-2'-deoxyguanosine; 8-Oxo-7,8-dihydrodeoxyguanosine; 8-Oxo-dG		| OtherNames=7,8-Dihydro-8-oxo-2'-deoxyguanosine; 7,8-Dihydro-8-oxodeoxyguanosine; 8-Hydroxy-2'-deoxyguanosine; 8-Hydroxydeoxyguanosine; 8-Oxo-2'-deoxyguanosine; 8-Oxo-7,8-dihydro-2'-deoxyguanosine; 8-Oxo-7,8-dihydrodeoxyguanosine; 8-Oxo-dG; 8-OH-dG
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			'''8-Oxo-2'-deoxyguanosine''' ('''8-oxo-dG''') is an oxidized derivative of ]. 8-Oxo-dG is one of the major products of ].<ref>{{cite journal | journal = Cancer Research | volume = 61 | pages = 5378–5381 |date=July 2001 | title = Repair of 8-Oxodeoxyguanosine Lesions in Mitochondrial DNA Depends on the Oxoguanine DNA Glycosylase (OGG1) Gene and 8-Oxoguanine Accumulates in the Mitochondrial DNA of OGG1-defective Mice | author = Nadja C. de Souza-Pinto | author2 = Lars Eide | author3 = Barbara A. Hogue| author4 = Tanja Thybo | author5 = Tinna Stevnsner| author6 = Erling Seeberg | author7 = Arne Klungland | author8 = Vilhelm A. Bohr | name-list-style = amp | pmid = 11454679 | issue = 14}}</ref> Concentrations of 8-oxo-dG within a cell are a measurement of ].
			==In DNA==
			]
			Steady-state levels of DNA damages represent the balance between formation and repair. Swenberg et al.<ref>{{Cite journal |doi = 10.1093/toxsci/kfq371|pmid = 21163908|pmc = 3043087|title = Endogenous versus Exogenous DNA Adducts: Their Role in Carcinogenesis, Epidemiology, and Risk Assessment|year = 2011|last1 = Swenberg|first1 = J. A.|last2 = Lu|first2 = K.|last3 = Moeller|first3 = B. C.|last4 = Gao|first4 = L.|last5 = Upton|first5 = P. B.|last6 = Nakamura|first6 = J.|last7 = Starr|first7 = T. B.|journal = Toxicological Sciences|volume = 120| issue=Suppl 1 |pages = S130–S145}}</ref> measured average frequencies of steady state endogenous ]s in mammalian cells. The most frequent oxidative DNA damage normally present in DNA is 8-oxo-dG, occurring at an average frequency of 2,400 per cell.
			When 8-oxo-dG is induced by a DNA damaging agent it is rapidly repaired. For example, 8-oxo-dG was increased 10-fold in the livers of mice subjected to ], but the excess 8-oxo-dG was rapidly removed with a ] of 11 minutes.<ref name="pmid11353081">{{cite journal |vauthors=Hamilton ML, Guo Z, Fuller CD, Van Remmen H, Ward WF, Austad SN, Troyer DA, Thompson I, Richardson A |title=A reliable assessment of 8-oxo-2-deoxyguanosine levels in nuclear and mitochondrial DNA using the sodium iodide method to isolate DNA |journal=Nucleic Acids Res. |volume=29 |issue=10 |pages=2117–26 |year=2001 |pmid=11353081 |pmc=55450 |doi= 10.1093/nar/29.10.2117}}</ref>
			As reviewed by Valavanidis et al.<ref name=Valavanidis>{{cite journal |vauthors=Valavanidis A, Vlachogianni T, Fiotakis K, Loridas S |title=Pulmonary oxidative stress, inflammation and cancer: respirable particulate matter, fibrous dusts and ozone as major causes of lung carcinogenesis through reactive oxygen species mechanisms |journal=Int J Environ Res Public Health |volume=10 |issue=9 |pages=3886–907 |year=2013 |pmid=23985773 |pmc=3799517 |doi=10.3390/ijerph10093886 |doi-access=free }}</ref> increased levels of 8-oxo-dG in a tissue can serve as a ] of oxidative stress. They also noted that increased levels of 8-oxo-dG are frequently found during ].
			In the figure shown in this section, the colonic ] from a mouse on a normal diet has a low level of 8-oxo-dG in its colonic crypts (panel A). However, a mouse likely undergoing colonic tumorigenesis (due to ] added to its diet<ref name=Prasad />) has a high level of 8-oxo-dG in its colonic epithelium (panel B). Deoxycholate increases intracellular production of reactive oxygen resulting in increased oxidative stress,<ref>{{Cite journal |doi = 10.1177/1535370214538743|pmid = 24951470|pmc = 4357421|title = Bile acid dysregulation, gut dysbiosis, and gastrointestinal cancer|year = 2014|last1 = Tsuei|first1 = Jessica|last2 = Chau|first2 = Thinh|last3 = Mills|first3 = David|last4 = Wan|first4 = Yu-Jui Yvonne|journal = Experimental Biology and Medicine|volume = 239|issue = 11|pages = 1489–1504}}</ref><ref>{{Cite journal |doi = 10.1186/1477-7819-12-164|pmid = 24884764|pmc = 4041630|title = Secondary bile acids: An underrecognized cause of colon cancer|year = 2014|last1 = Ajouz|first1 = Hana|last2 = Mukherji|first2 = Deborah|last3 = Shamseddine|first3 = Ali|journal = World Journal of Surgical Oncology|volume = 12|pages = 164 | doi-access=free }}</ref> and this leads to tumorigenesis and ]. Of 22 mice fed the diet supplemented with ], 20 (91%) developed colonic tumors after 10 months on the diet, and the tumors in 10 of these mice (45% of mice) included an adenocarcinoma (cancer).<ref name=Prasad />
			==In aging==
			8-oxo-dG increases with age in DNA of mammalian tissues.<ref name="pmid23738036">{{cite journal |vauthors=Nie B, Gan W, Shi F, Hu GX, Chen LG, Hayakawa H, Sekiguchi M, Cai JP |title=Age-dependent accumulation of 8-oxoguanine in the DNA and RNA in various rat tissues |journal=Oxid Med Cell Longev |volume=2013 |pages=303181 |year=2013 |pmid=23738036 |pmc=3657452 |doi=10.1155/2013/303181 |doi-access=free }}</ref> 8-oxo-dG increases in both ] and ] with age.<ref name="pmid11517304">{{cite journal |vauthors=Hamilton ML, Van Remmen H, Drake JA, Yang H, Guo ZM, Kewitt K, Walter CA, Richardson A |title=Does oxidative damage to DNA increase with age? |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=98 |issue=18 |pages=10469–74 |year=2001 |pmid=11517304 |pmc=56984 |doi=10.1073/pnas.171202698 |bibcode=2001PNAS...9810469H |doi-access=free }}</ref> Fraga et al.<ref name="pmid2352934">{{cite journal |vauthors=Fraga CG, Shigenaga MK, Park JW, Degan P, Ames BN |title=Oxidative damage to DNA during aging: 8-hydroxy-2'-deoxyguanosine in rat organ DNA and urine |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=87 |issue=12 |pages=4533–7 |year=1990 |pmid=2352934 |pmc=54150 |doi= 10.1073/pnas.87.12.4533|bibcode=1990PNAS...87.4533F |doi-access=free }}</ref> estimated that in rat kidney, for every 54 residues of 8-oxo-dG repaired, one residue remains unrepaired. (See also ].)
			==In carcinogenesis==
			Increased oxidant stress inactivates temporarily the enzyme ] (Oxoguanine glycosylase) at sites with 8-oxo-dG, which recruits ] ] to the promoter DNA sequences of inflammatory genes, and activates ], inducing mechanisms of innate immunity that contribute to lung carcinogenesis.<ref>{{Cite journal|pmc = 6504182|year = 2019|last1 = Vlahopoulos|first1 = S.|last2 = Adamaki|first2 = M.|last3 = Khoury|first3 = N.|last4 = Zoumpourlis|first4 = V.|last5 = Boldogh|first5 = I.|title = Roles of DNA repair enzyme OGG1 in innate immunity and its significance for lung cancer|journal = Pharmacology & Therapeutics|volume = 194|pages = 59–72|doi = 10.1016/j.pharmthera.2018.09.004|pmid = 30240635}}</ref>
			Valavanidis et al.<ref name=Valavanidis /> pointed out that oxidative DNA damage, such as 8-oxo-dG, likely contributes to carcinogenesis by two mechanisms. The first mechanism involves modulation of gene expression, whereas the second is through the induction of mutations.
			In individuals with chronic ] virus infection, increased expression of 8-oxo-dG is a risk factor for the development of ].<ref>Chuma M, Hige S, Nakanishi M, Ogawa K, Natsuizaka M, Yamamoto Y, Asaka M. 8-Hydroxy-2'-deoxy-guanosine is a risk factor for development of hepatocellular carcinoma in patients with chronic hepatitis C virus infection. J Gastroenterol Hepatol. 2008 Sep;23(9):1431-6. doi: 10.1111/j.1440-1746.2008.05502.x. PMID: 18854000</ref><ref>Shimoda R, Nagashima M, Sakamoto M, Yamaguchi N, Hirohashi S, Yokota J, Kasai H. Increased formation of oxidative DNA damage, 8-hydroxydeoxyguanosine, in human livers with chronic hepatitis. Cancer Res. 1994 Jun 15;54(12):3171-2. PMID: 8205535</ref>
			===Epigenetic alterations===
			], for instance by ] in a promoter region of a gene, can repress expression of the gene (see ]). In general, epigenetic alteration can modulate gene expression. As reviewed by Bernstein and Bernstein,<ref name=Bernstein2015>{{cite journal |vauthors=Bernstein C, Bernstein H |title=Epigenetic reduction of DNA repair in progression to gastrointestinal cancer |journal=World J Gastrointest Oncol |volume=7 |issue=5 |pages=30–46 |year=2015 |pmid=25987950 |pmc=4434036 |doi=10.4251/wjgo.v7.i5.30 |doi-access=free }}</ref> the repair of various types of DNA damages can, with low frequency, leave remnants of the different repair processes and thereby cause epigenetic alterations. 8-Oxo-dG is primarily repaired by ] (BER).<ref name="pmid23901781">{{cite journal |vauthors=Scott TL, Rangaswamy S, Wicker CA, Izumi T |title=Repair of oxidative DNA damage and cancer: recent progress in DNA base excision repair |journal=Antioxid. Redox Signal. |volume=20 |issue=4 |pages=708–26 |year=2014 |pmid=23901781 |pmc=3960848 |doi=10.1089/ars.2013.5529 }}</ref> Li et al.<ref name="pmid23311711">{{cite journal |vauthors=Li J, Braganza A, Sobol RW |title=Base excision repair facilitates a functional relationship between Guanine oxidation and histone demethylation |journal=Antioxid. Redox Signal. |volume=18 |issue=18 |pages=2429–43 |year=2013 |pmid=23311711 |pmc=3671628 |doi=10.1089/ars.2012.5107 }}</ref> reviewed studies indicating that one or more BER proteins also participate(s) in epigenetic alterations involving DNA methylation, demethylation or reactions coupled to histone modification. Nishida et al.<ref name="pmid24281021">{{cite journal |vauthors=Nishida N, Arizumi T, Takita M, Kitai S, Yada N, Hagiwara S, Inoue T, Minami Y, Ueshima K, Sakurai T, Kudo M |title=Reactive oxygen species induce epigenetic instability through the formation of 8-hydroxydeoxyguanosine in human hepatocarcinogenesis |journal=Dig Dis |volume=31 |issue=5–6 |pages=459–66 |year=2013 |pmid=24281021 |doi=10.1159/000355245 |doi-access=free }}</ref> examined 8-oxo-dG levels and also evaluated promoter methylation of 11 tumor suppressor genes (TSGs) in 128 liver biopsy samples. These biopsies were taken from patients with chronic hepatitis C, a condition causing oxidative damages in the liver. Among 5 factors evaluated, only increased levels of 8-oxo-dG was highly correlated with promoter methylation of TSGs (p<0.0001). This promoter methylation could have reduced expression of these tumor suppressor genes and contributed to ].
			===Mutagenesis===
			Yasui et al.<ref name="pmid24559511">{{cite journal |vauthors=Yasui M, Kanemaru Y, Kamoshita N, Suzuki T, Arakawa T, Honma M |title=Tracing the fates of site-specifically introduced DNA adducts in the human genome |journal=DNA Repair (Amst.) |volume=15 |pages=11–20 |year=2014 |pmid=24559511 |doi=10.1016/j.dnarep.2014.01.003 |doi-access=free }}</ref> examined the fate of 8-oxo-dG when this oxidized derivative of ] was inserted into the ] gene in a chromosome within human lymphoblastoid cells in culture. They inserted 8-oxo-dG into about 800 cells, and could detect the products that occurred after the insertion of this altered base, as determined from the clones produced after growth of the cells.
			8-Oxo-dG was restored to G in 86% of the clones, probably reflecting accurate ] or ] without mutation. G:C to T:A ]s occurred in 5.9% of the clones, single base ] in 2.1% and G:C to C:G transversions in 1.2%. Together, these more common mutations totaled 9.2% of the 14% of mutations generated at the site of the 8-oxo-dG insertion. Among the other mutations in the 800 clones analyzed, there were also 3 larger deletions, of sizes 6, 33 and 135 base pairs. Thus 8-oxo-dG, if not repaired, can directly cause frequent mutations, some of which may contribute to ].
			==In memory formation==
			Two reviews<ref name="pmid20649473">{{cite journal |vauthors=Massaad CA, Klann E |title=Reactive oxygen species in the regulation of synaptic plasticity and memory |journal=Antioxid. Redox Signal. |volume=14 |issue=10 |pages=2013–54 |date=May 2011 |pmid=20649473 |pmc=3078504 |doi=10.1089/ars.2010.3208 }}</ref><ref name="pmid27625575">{{cite journal |vauthors=Beckhauser TF, Francis-Oliveira J, De Pasquale R |title=Reactive Oxygen Species: Physiological and Physiopathological Effects on Synaptic Plasticity |journal=J Exp Neurosci |volume=10 |issue=Suppl 1 |pages=23–48 |date=2016 |pmid=27625575 |pmc=5012454 |doi=10.4137/JEN.S39887 }}</ref> summarize the large body of evidence, reported largely between 1996 and 2011, for the critical and essential role of ROS in ] formation. A recent additional body of evidence indicates that both the formation and storage of memory depend on ] modifications in neurons, including alterations in neuronal ].<ref name="pmid21116250">{{cite journal |vauthors=Day JJ, Sweatt JD |title=Epigenetic modifications in neurons are essential for formation and storage of behavioral memory |journal=Neuropsychopharmacology |volume=36 |issue=1 |pages=357–8 |date=January 2011 |pmid=21116250 |pmc=3055499 |doi=10.1038/npp.2010.125 }}</ref><ref name="pmid26875778">{{cite journal |vauthors=Sweatt JD |title=Neural plasticity and behavior - sixty years of conceptual advances |journal=J. Neurochem. |volume=139 |pages=179–199 |date=October 2016 |issue=Suppl 2 |pmid=26875778 |doi=10.1111/jnc.13580 |doi-access=free }}</ref> The two bodies of information on memory formation appear to be connected in 2016 by the work of Zhou et al,<ref name=Zhou>{{cite journal |vauthors=Zhou X, Zhuang Z, Wang W, He L, Wu H, Cao Y, Pan F, Zhao J, Hu Z, Sekhar C, Guo Z |title=OGG1 is essential in oxidative stress induced DNA demethylation |journal=Cell. Signal. |volume=28 |issue=9 |pages=1163–71 |date=September 2016 |pmid=27251462 |doi=10.1016/j.cellsig.2016.05.021 }}</ref> who showed that 8-oxo-dG, a major product of ROS interaction with DNA,<ref name="pmid22750987">{{cite journal |vauthors=Jena NR |title=DNA damage by reactive species: Mechanisms, mutation and repair |journal=J. Biosci. |volume=37 |issue=3 |pages=503–17 |date=July 2012 |pmid=22750987 |doi= 10.1007/s12038-012-9218-2|s2cid=14837181 }}</ref><ref name=BaBoldogh>{{cite journal |vauthors=Ba X, Boldogh I |title=8-Oxoguanine DNA glycosylase 1: Beyond repair of the oxidatively modified base lesions |journal=Redox Biol |volume=14 |pages=669–678 |date=April 2018 |pmid=29175754 |pmc=5975208 |doi=10.1016/j.redox.2017.11.008 }}</ref> has a central role in epigenetic ].
			The activation of transcription of some genes by transcription factors depends on the presence of 8-oxo-dG in the promoter regions and its recognition by the DNA repair glycosylase OGG1.<ref name="pmid27871818">{{cite journal |vauthors=Seifermann M, Epe B |title=Oxidatively generated base modifications in DNA: Not only carcinogenic risk factor but also regulatory mark? |journal=Free Radic. Biol. Med. |volume=107 |pages=258–265 |date=June 2017 |pmid=27871818 |doi=10.1016/j.freeradbiomed.2016.11.018 }}</ref><ref name=BaBoldogh />
			As reviewed by Duke et al., neuron DNA methylation and demethylation are altered by neuronal activity. Active DNA methylations and demethylations are required for ], are modified by experiences, and are required for memory formation and maintenance.<ref name=Duke>{{cite journal |vauthors=Duke CG, Kennedy AJ, Gavin CF, Day JJ, Sweatt JD |title=Experience-dependent epigenomic reorganization in the hippocampus |journal=Learn. Mem. |volume=24 |issue=7 |pages=278–288 |date=July 2017 |pmid=28620075 |pmc=5473107 |doi=10.1101/lm.045112.117 }}</ref>
			In mammals, ]s (which add ]s to DNA bases) exhibit a strong sequence preference for cytosines within the particular DNA sequence cytosine-phosphate-guanine (]s).<ref name=Ziller>{{cite journal |vauthors=Ziller MJ, Müller F, Liao J, Zhang Y, Gu H, Bock C, Boyle P, Epstein CB, Bernstein BE, Lengauer T, Gnirke A, Meissner A |title=Genomic distribution and inter-sample variation of non-CpG methylation across human cell types |journal=PLOS Genet. |volume=7 |issue=12 |pages=e1002389 |date=December 2011 |pmid=22174693 |pmc=3234221 |doi=10.1371/journal.pgen.1002389 |doi-access=free }}</ref> In the mouse brain, 4.2% of all cytosines are methylated, primarily in the context of CpG sites, forming 5mCpG.<ref name=Fasolino>{{cite journal |vauthors=Fasolino M, Zhou Z |title=The Crucial Role of DNA Methylation and MeCP2 in Neuronal Function |journal=Genes (Basel) |volume=8 |issue=5 |pages= 141|date=May 2017 |pmid=28505093 |pmc=5448015 |doi=10.3390/genes8050141 |doi-access=free }}</ref> Most hypermethylated 5mCpG sites increase the repression of associated genes.<ref name=Fasolino /> As shown by Zhou et al.,<ref name=Zhou /> and illustrated below, oxidation of the guanine in the methylated CpG site, to form 5mCp-8-oxo-dG is the first step in demethylation.
			8-oxo-dG complexed with OGG1 likely has a major role in facilitating thousands of rapid demethylations of methylated cytosines in ]s during formation of memory and further demethylations (over a period of weeks) during ]. As shown in 2016 by Halder et al.<ref name="pmid26656643">{{cite journal |vauthors=Halder R, Hennion M, Vidal RO, Shomroni O, Rahman RU, Rajput A, Centeno TP, van Bebber F, Capece V, Garcia Vizcaino JC, Schuetz AL, Burkhardt S, Benito E, Navarro Sala M, Javan SB, Haass C, Schmid B, Fischer A, Bonn S |title=DNA methylation changes in plasticity genes accompany the formation and maintenance of memory |journal=Nat. Neurosci. |volume=19 |issue=1 |pages=102–10 |date=January 2016 |pmid=26656643 |pmc=4700510 |doi=10.1038/nn.4194 }}</ref> using mice, and in 2017 by Duke et al.<ref name=Duke /> using rats, when contextual ] is applied to the rodents, causing an especially strong ] to form, within hours there are thousands of methylations and demethylations in the hippocampus brain region neurons. As shown with the rats, 9.2% of the genes in the rat ] neurons are differentially methylated. In mice, examined at 4 weeks after conditioning, the hippocampus methylations and demethylations were reversed (the hippocampus is needed to form memories but memories are not stored there) while substantial differential CpG methylation and demethylation occurred in ] neurons during memory maintenance. There were 1,223 differentially methylated genes in the anterior cingulate cortex of mice four weeks after contextual fear conditioning. Where demethylations occur, oxidation of the guanine in the CpG site to form 8-oxo-dG is an important first step.<ref name=Zhou />
			===Demethylation at CpG sites requires 8-oxo-dG===
			] at a ]. In adult somatic cells DNA methylation typically occurs in the context of CpG dinucleotides (]), forming ]-pG, or 5mCpG. Reactive oxygen species (ROS) may attack guanine at the dinucleotide site, forming ] (8-OHdG), and resulting in a 5mCp-8-OHdG dinucleotide site. The ] enzyme ] targets 8-OHdG and binds to the lesion without immediate excision. OGG1, present at a 5mCp-8-OHdG site recruits ] and TET1 oxidizes the 5mC adjacent to the 8-OHdG. This initiates demethylation of 5mC.<ref name=Zhou/>]]
			] (5mC) in neuron DNA. As reviewed in 2018,<ref name="pmid29875631">{{cite journal |vauthors=Bayraktar G, Kreutz MR |title=The Role of Activity-Dependent DNA Demethylation in the Adult Brain and in Neurological Disorders |journal=Front Mol Neurosci |volume=11 |pages=169 |date=2018 |pmid=29875631 |pmc=5975432 |doi=10.3389/fnmol.2018.00169 |doi-access=free }}</ref> in brain neurons, 5mC is oxidized by the ten-eleven translocation (TET) family of dioxygenases (], ], ]) to generate ] (5hmC). In successive steps TET enzymes further hydroxylate 5hmC to generate 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). ] (TDG) recognizes the intermediate bases 5fC and 5caC and excises the ] resulting in an apyrimidinic site (]). In an alternative oxidative deamination pathway, 5hmC can be oxidatively deaminated by activity-induced cytidine deaminase/apolipoprotein B mRNA editing complex ] deaminases to form 5-hydroxymethyluracil (5hmU) or 5mC can be converted to ] (Thy). 5hmU can be cleaved by TDG, single-strand-selective monofunctional uracil-DNA glycosylase 1 (]), Nei-Like DNA Glycosylase 1 (]), or methyl-CpG binding protein 4 (]). AP sites and T:G mismatches are then repaired by base excision repair (BER) enzymes to yield ] (Cyt).]]
			] is a key enzyme involved in demethylating 5mCpG. However, TET1 is only able to act on 5mCpG if an ROS has first acted on the guanine to form ] (8-OHdG or its tautomer 8-oxo-dG), resulting in a 5mCp-8-OHdG dinucleotide (see first figure in this section).<ref name=Zhou /> After formation of 5mCp-8-OHdG, the ] enzyme ] binds to the 8-OHdG lesion without immediate excision. Adherence of OGG1 to the 5mCp-8-OHdG site recruits ], allowing TET1 to oxidize the 5mC adjacent to 8-OHdG, as shown in the first figure in this section. This initiates the demethylation pathway shown in the second figure in this section.
			Altered protein expression in neurons, controlled by 8-oxo-dG-dependent demethylation of CpG sites in gene promoters within neuron DNA, is central to memory formation.<ref name="pmid20975755">{{cite journal |vauthors=Day JJ, Sweatt JD |title=DNA methylation and memory formation |journal=Nat. Neurosci. |volume=13 |issue=11 |pages=1319–23 |date=November 2010 |pmid=20975755 |pmc=3130618 |doi=10.1038/nn.2666 }}</ref>
			== See also ==
			* ]
			* ]
			==References==
			{{reflist}}
			{{DEFAULTSORT:Oxo-2'-deoxyguanosine, 8-}}
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