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| '''''dnaQ''''' is the gene encoding the ε subunit of ] in '']''.<ref>{{cite journal| |
'''''dnaQ''''' is the gene encoding the ε subunit of ] in '']''.<ref>{{cite journal | vauthors = Scheuermann R, Tam S, Burgers PM, Lu C, Echols H | title = Identification of the epsilon-subunit of Escherichia coli DNA polymerase III holoenzyme as the dnaQ gene product: a fidelity subunit for DNA replication | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 80 | issue = 23 | pages = 7085–9 | date = December 1983 | pmid = 6359162 | pmc = 389997 | doi = 10.1073/pnas.80.23.7085 }}</ref> The ε subunit is one of three core proteins in the DNA polymerase complex. It functions as a 3’→5’ DNA directed ] ] that removes incorrectly incorporated bases during replication.<ref>{{cite journal | vauthors = Scheuermann RH, Echols H | title = A separate editing exonuclease for DNA replication: the epsilon subunit of Escherichia coli DNA polymerase III holoenzyme | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 81 | issue = 24 | pages = 7747–51 | date = December 1984 | pmid = 6393125 | pmc = 392229 | doi = 10.1073/pnas.81.24.7747 }}</ref> ''dnaQ'' may also be referred to as ''mutD''.<ref>{{cite book | last1 = Kornberg | first1 = Arthur | last2 = Baker | first2 = Tania | name-list-format = vanc | title=DNA Replication|date=2005|publisher=University Science Books|location=California|isbn=1-891389-44-0|page=499|edition=2nd}}</ref> | ||
| ==Biological Role== | ==Biological Role== | ||
| Missense mutations in the ''dnaQ'' gene lead to the induction of the ] mechanism. Mutating the essential amino acid in the catalytic center of the ε subunit leads to complete loss of function.<ref>{{cite journal| |
Missense mutations in the ''dnaQ'' gene lead to the induction of the ] mechanism. Mutating the essential amino acid in the catalytic center of the ε subunit leads to complete loss of function.<ref>{{cite journal | vauthors = Gautam S, Kalidindi R, Humayun MZ | title = SOS induction and mutagenesis by dnaQ missense alleles in wild type cells | journal = Mutation Research | volume = 735 | issue = 1-2 | pages = 46–50 | date = July 2012 | pmid = 22677460 | doi = 10.1016/j.mrfmmm.2012.05.004 }}</ref> | ||
| Overexpression of the ε subunit decreases the incidence of mutations with exposure to UV, proving that the epsilon subunit has an essential function in DNA editing and preventing the initiation of SOS DNA repair.<ref>{{cite journal| |
Overexpression of the ε subunit decreases the incidence of mutations with exposure to UV, proving that the epsilon subunit has an essential function in DNA editing and preventing the initiation of SOS DNA repair.<ref>{{cite journal | vauthors = Jonczyk P, Fijalkowska I, Ciesla Z | title = Overproduction of the epsilon subunit of DNA polymerase III counteracts the SOS mutagenic response of Escherichia coli | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 85 | issue = 23 | pages = 9124–7 | date = December 1988 | pmid = 3057500 | pmc = 282676 | doi = 10.1073/pnas.85.23.9124 }}</ref> | ||
| The ε subunit has also been proven to have some impact on the growth rate of E. coli. Silencing of the ''dnaQ'' gene is correlated to significantly reduced growth.<ref>{{cite journal| |
The ε subunit has also been proven to have some impact on the growth rate of E. coli. Silencing of the ''dnaQ'' gene is correlated to significantly reduced growth.<ref>{{cite journal | vauthors = Stefan A, Reggiani L, Cianchetta S, Radeghieri A, Gonzalez Vara y Rodriguez A, Hochkoeppler A | title = Silencing of the gene coding for the epsilon subunit of DNA polymerase III slows down the growth rate of Escherichia coli populations | journal = FEBS Letters | volume = 546 | issue = 2-3 | pages = 295–9 | date = July 2003 | pmid = 12832057 | doi = 10.1016/S0014-5793(03)00604-5 }}</ref> | ||
| ==Interactions== | == Interactions == | ||
| The ε subunit is stabilized by the θ subunit within the complete polymerase complex.<ref>{{cite journal|last1=Taft-Benz|first1=Sharon A.|last2=Schaaper|first2=Roel M.|title=The θ Subunit of Escherichia coli DNA Polymerase III: a Role in Stabilizing the ε Proofreading Subunit|journal=J. Bacteriol.|date=May 2004|volume=186|issue=9|pages=2774–2780|doi=10.1128/JB.186.9.2774-2780.2004}}</ref> | |||
| The |
The ε subunit is stabilized by the θ subunit within the complete polymerase complex.<ref>{{cite journal | vauthors = Taft-Benz SA, Schaaper RM | title = The theta subunit of Escherichia coli DNA polymerase III: a role in stabilizing the epsilon proofreading subunit | journal = Journal of Bacteriology | volume = 186 | issue = 9 | pages = 2774–80 | date = May 2004 | pmid = 15090519 | doi = 10.1128/JB.186.9.2774-2780.2004 }}</ref> | ||
| The gene encodes two functional domains: the N-terminus of the gene product binds the θ subunit and carries out the exonuclease function and the C-terminus binds the α subunit responsible for polymerase activity.<ref>{{cite journal | vauthors = Taft-Benz SA, Schaaper RM | title = The C-terminal domain of dnaQ contains the polymerase binding site | journal = Journal of Bacteriology | volume = 181 | issue = 9 | pages = 2963–5 | date = May 1999 | pmid = 10217794 }}</ref> | |||
| ⚫ | A Q-linker peptide of 22 residues has been identified that links the α subunit to the ε subunit, conferring flexibility that sets the α:ε complex apart from other more restricted multi-domain proofreading polymerases.<ref>{{cite journal| |
||
| ⚫ | A Q-linker peptide of 22 residues has been identified that links the α subunit to the ε subunit, conferring flexibility that sets the α:ε complex apart from other more restricted multi-domain proofreading polymerases.<ref>{{cite journal | vauthors = Ozawa K, Jergic S, Park AY, Dixon NE, Otting G | title = The proofreading exonuclease subunit epsilon of Escherichia coli DNA polymerase III is tethered to the polymerase subunit alpha via a flexible linker | journal = Nucleic Acids Research | volume = 36 | issue = 15 | pages = 5074–82 | date = September 2008 | pmid = 18663010 | doi = 10.1093/nar/gkn489 }}</ref><ref>{{cite journal | vauthors = Ozawa K, Horan NP, Robinson A, Yagi H, Hill FR, Jergic S, Xu ZQ, Loscha KV, Li N, Tehei M, Oakley AJ, Otting G, Huber T, Dixon NE | title = Proofreading exonuclease on a tether: the complex between the E. coli DNA polymerase III subunits α, epsilon, θ and β reveals a highly flexible arrangement of the proofreading domain | journal = Nucleic Acids Research | volume = 41 | issue = 10 | pages = 5354–67 | date = May 2013 | pmid = 23580545 | doi = 10.1093/nar/gkt162 }}</ref> | ||
| There is interaction between the missense suppressor glycine tRNA encoded by the ''mutA'' gene that is correlated to significantly increased mutation rate in cells that express the gene. The uncharged MutA tRNA possesses complementarity to a region in the 5' end of the ''dnaQ'' mRNA. This allows it to act as an antisense mRNA that directs the degradation of the dnaQ transcript and thus, a lower abundance of the subunit and increased frequency of mutation.<ref>{{cite journal|last1=Dorazi|first1=Robert|title=Can tRNAs act as antisense RNA? The case of mutA and dnaQ|journal=J. Theor. Biol.|date=7 December 2003|volume=225|issue=3|pages=383–388|doi=10.1016/S0022-5193(03)00268-6}}</ref> More recently, it was suggested that the tRNA directs replacement of essential glutamate residues with glycine, leading to aberrant ε subunits and resulting in an increase in mutations. Studies with T4 bacteriophage and ''E. coli'' with defective ''dnaQ'' genes give evidence that the mutA tRNA may not have any effect on the transcription of the ''dnaQ'' gene but may affect the translation of the gene product.<ref>{{cite journal|last1=Al Mamun|first1=Abu Amar M.|last2=Gautam|first2=Satyendra|last3=Humayun|first3=M. Zafri|title=Hypermutagenesis in mutA cells is mediated by mistranslational corruption of polymerase, and is accompanied by replication fork collapse|journal=Mol. Micro.|date=1 November 2006|volume=62|issue=6|pages=1752–1763|doi=10.1111/j.1365-2958.2006.05490.x}}</ref> | There is interaction between the missense suppressor glycine tRNA encoded by the ''mutA'' gene that is correlated to significantly increased mutation rate in cells that express the gene. The uncharged MutA tRNA possesses complementarity to a region in the 5' end of the ''dnaQ'' mRNA. This allows it to act as an antisense mRNA that directs the degradation of the dnaQ transcript and thus, a lower abundance of the subunit and increased frequency of mutation.<ref>{{cite journal|last1=Dorazi|first1=Robert|title=Can tRNAs act as antisense RNA? The case of mutA and dnaQ|journal=J. Theor. Biol.|date=7 December 2003|volume=225|issue=3|pages=383–388|doi=10.1016/S0022-5193(03)00268-6}}</ref> More recently, it was suggested that the tRNA directs replacement of essential glutamate residues with glycine, leading to aberrant ε subunits and resulting in an increase in mutations. Studies with T4 bacteriophage and ''E. coli'' with defective ''dnaQ'' genes give evidence that the mutA tRNA may not have any effect on the transcription of the ''dnaQ'' gene but may affect the translation of the gene product.<ref>{{cite journal|last1=Al Mamun|first1=Abu Amar M.|last2=Gautam|first2=Satyendra|last3=Humayun|first3=M. Zafri|title=Hypermutagenesis in mutA cells is mediated by mistranslational corruption of polymerase, and is accompanied by replication fork collapse|journal=Mol. Micro.|date=1 November 2006|volume=62|issue=6|pages=1752–1763|doi=10.1111/j.1365-2958.2006.05490.x}}</ref> | ||
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| Sequences have been found in other organisms that encode gene products with a similar function to ''dnaQ'': | Sequences have been found in other organisms that encode gene products with a similar function to ''dnaQ'': | ||
| In ''Mycobaterium tuberculosis'', the gene ''dnaE1'' encodes a polymerase and ] (PHP) domain that carries out the 3’→5’ exonuclease and proofreading function.<ref>{{cite journal|last1=Du Toit|first1=Andrea|title=An ancient mycobacterial proofreader|journal=Nature Reviews Microbiology|date=6 May 2015|volume=13|issue=329|doi=10.1038/nrmicro3493 |
In ''Mycobaterium tuberculosis'', the gene ''dnaE1'' encodes a polymerase and ] (PHP) domain that carries out the 3’→5’ exonuclease and proofreading function.<ref>{{cite journal|last1=Du Toit|first1=Andrea | name-list-format = vanc | title = An ancient mycobacterial proofreader|journal=Nature Reviews Microbiology|date=6 May 2015|volume=13|issue=329|doi=10.1038/nrmicro3493 }}</ref> | ||
| ''TREX1'' is the major 3'→5' exonuclease in humans. It is responsible for metabolizing both single stranded DNA (ssDNA) and double stranded DNA (dsDNA) with mismatched 3' ends and is directed by endogenous ].<ref>{{cite web|last1=The Unitprot Consortium|title=TREX1 - Three-prime repair exonuclease 1|url=http://www.uniprot.org/uniprot/Q9NSU2|website=UniprotKB| |
''TREX1'' is the major 3'→5' exonuclease in humans. It is responsible for metabolizing both single stranded DNA (ssDNA) and double stranded DNA (dsDNA) with mismatched 3' ends and is directed by endogenous ].<ref>{{cite web|last1=The Unitprot Consortium|title=TREX1 - Three-prime repair exonuclease 1|url=http://www.uniprot.org/uniprot/Q9NSU2|website=UniprotKB|access-date=9 November 2015}}</ref> Initially, ''TREX1'' was called DNase III because it showed sequence homology with ''dnaQ'' in E. coli and with eukaryotic DNA polymerase epsilon, and possesses biochemical characteristics that associate with the capability of DNA proofreading.<ref>{{cite journal | vauthors = Höss M, Robins P, Naven TJ, Pappin DJ, Sgouros J, Lindahl T | title = A human DNA editing enzyme homologous to the Escherichia coli DnaQ/MutD protein | journal = The EMBO Journal | volume = 18 | issue = 13 | pages = 3868–75 | date = July 1999 | pmid = 10393201 | pmc = 1171463 | doi = 10.1093/emboj/18.13.3868 }}</ref> | ||
| ==References== | == References == | ||
| {{reflist}} | {{reflist|32em}} | ||
| ==External links== | == External links == | ||
| * {{MeshName|dnaQ+protein,+E+coli}} | * {{MeshName|dnaQ+protein,+E+coli}} | ||
Revision as of 16:24, 20 March 2018
| DNA pol III epsilon subunit | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Organism | Escherichia coli (str. K-12 substr. MG1655) | ||||||
| Symbol | dnaQ | ||||||
| Entrez | 946441 | ||||||
| RefSeq (Prot) | NP_414751.1 | ||||||
| UniProt | P03007 | ||||||
| Other data | |||||||
| EC number | 2.7.7.7 | ||||||
| Chromosome | genome: 0.24 - 0.24 Mb | ||||||
| |||||||
dnaQ is the gene encoding the ε subunit of DNA polymerase III in Escherichia coli. The ε subunit is one of three core proteins in the DNA polymerase complex. It functions as a 3’→5’ DNA directed proofreading exonuclease that removes incorrectly incorporated bases during replication. dnaQ may also be referred to as mutD.
Biological Role
Missense mutations in the dnaQ gene lead to the induction of the SOS DNA repair mechanism. Mutating the essential amino acid in the catalytic center of the ε subunit leads to complete loss of function.
Overexpression of the ε subunit decreases the incidence of mutations with exposure to UV, proving that the epsilon subunit has an essential function in DNA editing and preventing the initiation of SOS DNA repair.
The ε subunit has also been proven to have some impact on the growth rate of E. coli. Silencing of the dnaQ gene is correlated to significantly reduced growth.
Interactions
The ε subunit is stabilized by the θ subunit within the complete polymerase complex.
The gene encodes two functional domains: the N-terminus of the gene product binds the θ subunit and carries out the exonuclease function and the C-terminus binds the α subunit responsible for polymerase activity.
A Q-linker peptide of 22 residues has been identified that links the α subunit to the ε subunit, conferring flexibility that sets the α:ε complex apart from other more restricted multi-domain proofreading polymerases.
There is interaction between the missense suppressor glycine tRNA encoded by the mutA gene that is correlated to significantly increased mutation rate in cells that express the gene. The uncharged MutA tRNA possesses complementarity to a region in the 5' end of the dnaQ mRNA. This allows it to act as an antisense mRNA that directs the degradation of the dnaQ transcript and thus, a lower abundance of the subunit and increased frequency of mutation. More recently, it was suggested that the tRNA directs replacement of essential glutamate residues with glycine, leading to aberrant ε subunits and resulting in an increase in mutations. Studies with T4 bacteriophage and E. coli with defective dnaQ genes give evidence that the mutA tRNA may not have any effect on the transcription of the dnaQ gene but may affect the translation of the gene product.
Related sequences
Sequences have been found in other organisms that encode gene products with a similar function to dnaQ:
In Mycobaterium tuberculosis, the gene dnaE1 encodes a polymerase and histidinol-phosphatase (PHP) domain that carries out the 3’→5’ exonuclease and proofreading function.
TREX1 is the major 3'→5' exonuclease in humans. It is responsible for metabolizing both single stranded DNA (ssDNA) and double stranded DNA (dsDNA) with mismatched 3' ends and is directed by endogenous retroelements. Initially, TREX1 was called DNase III because it showed sequence homology with dnaQ in E. coli and with eukaryotic DNA polymerase epsilon, and possesses biochemical characteristics that associate with the capability of DNA proofreading.
References
- Scheuermann R, Tam S, Burgers PM, Lu C, Echols H (December 1983). "Identification of the epsilon-subunit of Escherichia coli DNA polymerase III holoenzyme as the dnaQ gene product: a fidelity subunit for DNA replication". Proceedings of the National Academy of Sciences of the United States of America. 80 (23): 7085–9. doi:10.1073/pnas.80.23.7085. PMC 389997. PMID 6359162.
- Scheuermann RH, Echols H (December 1984). "A separate editing exonuclease for DNA replication: the epsilon subunit of Escherichia coli DNA polymerase III holoenzyme". Proceedings of the National Academy of Sciences of the United States of America. 81 (24): 7747–51. doi:10.1073/pnas.81.24.7747. PMC 392229. PMID 6393125.
- Kornberg, Arthur; Baker, Tania (2005). DNA Replication (2nd ed.). California: University Science Books. p. 499. ISBN 1-891389-44-0.
{{cite book}}: Unknown parameter|name-list-format=ignored (|name-list-style=suggested) (help) - Gautam S, Kalidindi R, Humayun MZ (July 2012). "SOS induction and mutagenesis by dnaQ missense alleles in wild type cells". Mutation Research. 735 (1–2): 46–50. doi:10.1016/j.mrfmmm.2012.05.004. PMID 22677460.
- Jonczyk P, Fijalkowska I, Ciesla Z (December 1988). "Overproduction of the epsilon subunit of DNA polymerase III counteracts the SOS mutagenic response of Escherichia coli". Proceedings of the National Academy of Sciences of the United States of America. 85 (23): 9124–7. doi:10.1073/pnas.85.23.9124. PMC 282676. PMID 3057500.
- Stefan A, Reggiani L, Cianchetta S, Radeghieri A, Gonzalez Vara y Rodriguez A, Hochkoeppler A (July 2003). "Silencing of the gene coding for the epsilon subunit of DNA polymerase III slows down the growth rate of Escherichia coli populations". FEBS Letters. 546 (2–3): 295–9. doi:10.1016/S0014-5793(03)00604-5. PMID 12832057.
- Taft-Benz SA, Schaaper RM (May 2004). "The theta subunit of Escherichia coli DNA polymerase III: a role in stabilizing the epsilon proofreading subunit". Journal of Bacteriology. 186 (9): 2774–80. doi:10.1128/JB.186.9.2774-2780.2004. PMID 15090519.
- Taft-Benz SA, Schaaper RM (May 1999). "The C-terminal domain of dnaQ contains the polymerase binding site". Journal of Bacteriology. 181 (9): 2963–5. PMID 10217794.
- Ozawa K, Jergic S, Park AY, Dixon NE, Otting G (September 2008). "The proofreading exonuclease subunit epsilon of Escherichia coli DNA polymerase III is tethered to the polymerase subunit alpha via a flexible linker". Nucleic Acids Research. 36 (15): 5074–82. doi:10.1093/nar/gkn489. PMID 18663010.
- Ozawa K, Horan NP, Robinson A, Yagi H, Hill FR, Jergic S, Xu ZQ, Loscha KV, Li N, Tehei M, Oakley AJ, Otting G, Huber T, Dixon NE (May 2013). "Proofreading exonuclease on a tether: the complex between the E. coli DNA polymerase III subunits α, epsilon, θ and β reveals a highly flexible arrangement of the proofreading domain". Nucleic Acids Research. 41 (10): 5354–67. doi:10.1093/nar/gkt162. PMID 23580545.
- Dorazi, Robert (7 December 2003). "Can tRNAs act as antisense RNA? The case of mutA and dnaQ". J. Theor. Biol. 225 (3): 383–388. doi:10.1016/S0022-5193(03)00268-6.
- Al Mamun, Abu Amar M.; Gautam, Satyendra; Humayun, M. Zafri (1 November 2006). "Hypermutagenesis in mutA cells is mediated by mistranslational corruption of polymerase, and is accompanied by replication fork collapse". Mol. Micro. 62 (6): 1752–1763. doi:10.1111/j.1365-2958.2006.05490.x.
- Du Toit, Andrea (6 May 2015). "An ancient mycobacterial proofreader". Nature Reviews Microbiology. 13 (329). doi:10.1038/nrmicro3493.
{{cite journal}}: Unknown parameter|name-list-format=ignored (|name-list-style=suggested) (help) - The Unitprot Consortium. "TREX1 - Three-prime repair exonuclease 1". UniprotKB. Retrieved 9 November 2015.
- Höss M, Robins P, Naven TJ, Pappin DJ, Sgouros J, Lindahl T (July 1999). "A human DNA editing enzyme homologous to the Escherichia coli DnaQ/MutD protein". The EMBO Journal. 18 (13): 3868–75. doi:10.1093/emboj/18.13.3868. PMC 1171463. PMID 10393201.
External links
- dnaQ+protein,+E+coli at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
| DNA replication (comparing prokaryotic to eukaryotic) | |||||||
|---|---|---|---|---|---|---|---|
| Initiation |
| ||||||
| Replication |
| ||||||
| Termination | |||||||