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'''DNA polymerase theta''' is an [[enzyme]] that in humans is encoded by the ''POLQ'' [[gene]].<ref name="pmid10395804">{{cite journal | vauthors = Sharief FS, Vojta PJ, Ropp PA, Copeland WC | title = Cloning and chromosomal mapping of the human DNA polymerase theta (POLQ), the eighth human DNA polymerase | journal = Genomics | volume = 59 | issue = 1 | pages = 90–6 |date=Aug 1999 | pmid = 10395804 | pmc = | doi = 10.1006/geno.1999.5843 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: POLQ polymerase (DNA directed), theta| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10721| accessdate = }}</ref> | '''DNA polymerase theta''' is an [[enzyme]] that in humans is encoded by the ''POLQ'' [[gene]].<ref name="pmid10395804">{{cite journal | vauthors = Sharief FS, Vojta PJ, Ropp PA, Copeland WC | title = Cloning and chromosomal mapping of the human DNA polymerase theta (POLQ), the eighth human DNA polymerase | journal = Genomics | volume = 59 | issue = 1 | pages = 90–6 |date=Aug 1999 | pmid = 10395804 | pmc = | doi = 10.1006/geno.1999.5843 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: POLQ polymerase (DNA directed), theta| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10721| accessdate = }}</ref> Current evidence suggests that this polymerase is involved in repair of DNA double-strand breaks in a process termed [[microhomology-mediated end joining]] (MMEJ) .<ref name="pmid27264557">{{cite journal | vauthors = Wood RD, Doublié S | title = DNA polymerase θ (POLQ), double-strand break repair, and cancer | journal = DNA Repair (Amst) | volume = 44 | pages = 22-32 |date=August 2016 | pmid = 27264557 | pmc = | doi = 10.1016/j.dnarep.2016.05.003 }}</ref> Most double-strand breaks are repaired by [[non-homologous end joining]] (NHEJ) or [[homology directed repair]] (HDR). MMEJ is a variant of NHEJ, but differs in that it lacks a requirement for the [[Ku (protein)|Ku]] heterodimer, and involves DNA ends with 3′ single-stranded overhangs.<ref name="pmid25275444">{{cite journal | vauthors = Yousefzadeh MJ, Wyatt DW, Mu Y, Hensley SC, Tomida J, Bylund GO, Doublié S, Johansson E, Ramsden DA, McBride KM, Wood RD | title = Mechanism of suppression of chromosomal instability by DNA polymerase POLQ | journal = PLoS Genet | volume = 10 | issue = 10 | pages = e1004654 |date=October 2014 | pmid = 25275444 | pmc = | doi = 10.1371/journal.pgen.1004654 }}</ref> Following annealing of short (i.e., a few nucleotides) regions on the DNA overhangs, DNA polymerase theta catalyzes template-dependent DNA synthesis across the broken ends, stabilizing the paired structure.<ref name="pmid25642960">{{cite journal | vauthors = Mateos-Gomez PA, Gong F, Nair N, Miller KM, Lazzerini-Denchi E, Sfeir A | title = Mammalian polymerase θ promotes alternative NHEJ and suppresses recombination | journal = Nature | volume = 518 | issue = 7538 | pages = 254-7 |year=2015 | pmid = 25642960 | pmc = | doi = 10.1038/nature14157 }}</ref><ref name="pmid25642963">{{cite journal | vauthors = Ceccaldi R, Liu JC, Amunugama R, Hajdu I, Primack B, Petalcorin MI, O'Connor KW, Konstantinopoulos PA, Elledge SJ, Boulton SJ, Yusufzai T, D'Andrea AD | title = Homologous-recombination-deficient tumours are dependent on Polθ-mediated repair | journal = Nature | volume = 518 | issue = 7538 | pages = 258-62 |year=2015 | pmid = 25642963 | pmc = | doi = 10.1038/nature14184 }}</ref> | ||
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Latest revision as of 20:08, 26 August 2018
This article needs more links to other articles to help integrate it into the encyclopedia. (June 2016) (Learn how and when to remove this template message) |
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DNA polymerase theta is an enzyme that in humans is encoded by the POLQ gene.[1][2] Current evidence suggests that this polymerase is involved in repair of DNA double-strand breaks in a process termed microhomology-mediated end joining (MMEJ) .[3] Most double-strand breaks are repaired by non-homologous end joining (NHEJ) or homology directed repair (HDR). MMEJ is a variant of NHEJ, but differs in that it lacks a requirement for the Ku heterodimer, and involves DNA ends with 3′ single-stranded overhangs.[4] Following annealing of short (i.e., a few nucleotides) regions on the DNA overhangs, DNA polymerase theta catalyzes template-dependent DNA synthesis across the broken ends, stabilizing the paired structure.[5][6]
References
- ↑ Sharief FS, Vojta PJ, Ropp PA, Copeland WC (Aug 1999). "Cloning and chromosomal mapping of the human DNA polymerase theta (POLQ), the eighth human DNA polymerase". Genomics. 59 (1): 90–6. doi:10.1006/geno.1999.5843. PMID 10395804.
- ↑ "Entrez Gene: POLQ polymerase (DNA directed), theta".
- ↑ Wood RD, Doublié S (August 2016). "DNA polymerase θ (POLQ), double-strand break repair, and cancer". DNA Repair (Amst). 44: 22–32. doi:10.1016/j.dnarep.2016.05.003. PMID 27264557.
- ↑ Yousefzadeh MJ, Wyatt DW, Mu Y, Hensley SC, Tomida J, Bylund GO, Doublié S, Johansson E, Ramsden DA, McBride KM, Wood RD (October 2014). "Mechanism of suppression of chromosomal instability by DNA polymerase POLQ". PLoS Genet. 10 (10): e1004654. doi:10.1371/journal.pgen.1004654. PMID 25275444.
- ↑ Mateos-Gomez PA, Gong F, Nair N, Miller KM, Lazzerini-Denchi E, Sfeir A (2015). "Mammalian polymerase θ promotes alternative NHEJ and suppresses recombination". Nature. 518 (7538): 254–7. doi:10.1038/nature14157. PMID 25642960.
- ↑ Ceccaldi R, Liu JC, Amunugama R, Hajdu I, Primack B, Petalcorin MI, O'Connor KW, Konstantinopoulos PA, Elledge SJ, Boulton SJ, Yusufzai T, D'Andrea AD (2015). "Homologous-recombination-deficient tumours are dependent on Polθ-mediated repair". Nature. 518 (7538): 258–62. doi:10.1038/nature14184. PMID 25642963.
Further reading
- Hogg M, Sauer-Eriksson AE, Johansson E (2012). "Promiscuous DNA synthesis by human DNA polymerase θ." Nucleic Acids Research. 40 (6): 2611–2622. doi:10.1093/nar/gkr1102. PMC 3315306. PMID 22135286.
- Robertson NG, Khetarpal U, Gutiérrez-Espeleta GA, et al. (1995). "Isolation of novel and known genes from a human fetal cochlear cDNA library using subtractive hybridization and differential screening". Genomics. 23 (1): 42–50. doi:10.1006/geno.1994.1457. PMID 7829101.
- Maga G, Shevelev I, Ramadan K, et al. (2002). "DNA polymerase theta purified from human cells is a high-fidelity enzyme". J. Mol. Biol. 319 (2): 359–69. doi:10.1016/S0022-2836(02)00325-X. PMID 12051913.
- Seki M, Marini F, Wood RD (2003). "POLQ (Pol θ), a DNA polymerase and DNA-dependent ATPase in human cells". Nucleic Acids Res. 31 (21): 6117–26. doi:10.1093/nar/gkg814. PMC 275456. PMID 14576298.
- Kawamura K, Bahar R, Seimiya M, et al. (2004). "DNA polymerase theta is preferentially expressed in lymphoid tissues and upregulated in human cancers". Int. J. Cancer. 109 (1): 9–16. doi:10.1002/ijc.11666. PMID 14735462.
- Suzuki Y, Yamashita R, Shirota M, et al. (2004). "Sequence Comparison of Human and Mouse Genes Reveals a Homologous Block Structure in the Promoter Regions". Genome Res. 14 (9): 1711–8. doi:10.1101/gr.2435604. PMC 515316. PMID 15342556.
- Seki M, Masutani C, Yang LW, et al. (2005). "High-efficiency bypass of DNA damage by human DNA polymerase Q". EMBO J. 23 (22): 4484–94. doi:10.1038/sj.emboj.7600424. PMC 526458. PMID 15496986.
- Chiapperino D, Cai M, Sayer JM, et al. (2006). "Error-prone translesion synthesis by human DNA polymerase eta on DNA-containing deoxyadenosine adducts of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene". J. Biol. Chem. 280 (48): 39684–92. doi:10.1074/jbc.M508008200. PMID 16188888.
- Zan H, Shima N, Xu Z, et al. (2005). "The translesion DNA polymerase θ plays a dominant role in immunoglobulin gene somatic hypermutation". EMBO J. 24 (21): 3757–69. doi:10.1038/sj.emboj.7600833. PMC 1276717. PMID 16222339.
- Cruet-Hennequart S, Coyne S, Glynn MT, et al. (2006). "UV-induced RPA phosphorylation is increased in the absence of DNA polymerase eta and requires DNA-PK". DNA Repair (Amst.). 5 (4): 491–504. doi:10.1016/j.dnarep.2006.01.008. PMID 16520097.
- Chen YW, Cleaver JE, Hanaoka F, et al. (2006). "A novel role of DNA polymerase eta in modulating cellular sensitivity to chemotherapeutic agents". Mol. Cancer Res. 4 (4): 257–65. doi:10.1158/1541-7786.MCR-05-0118. PMID 16603639.
- Yuasa MS, Masutani C, Hirano A, et al. (2006). "A human DNA polymerase eta complex containing Rad18, Rad6 and Rev1; proteomic analysis and targeting of the complex to the chromatin-bound fraction of cells undergoing replication fork arrest". Genes Cells. 11 (7): 731–44. doi:10.1111/j.1365-2443.2006.00974.x. PMID 16824193.
- Choi JY, Stover JS, Angel KC, et al. (2006). "Biochemical basis of genotoxicity of heterocyclic arylamine food mutagens: Human DNA polymerase eta selectively produces a two-base deletion in copying the N2-guanyl adduct of 2-amino-3-methylimidazo[4,5-f]quinoline but not the C8 adduct at the NarI G3 site". J. Biol. Chem. 281 (35): 25297–306. doi:10.1074/jbc.M605699200. PMID 16835218.
- Kino K, Ito N, Sugasawa K, et al. (2007). "Translesion synthesis by human DNA polymerase eta across oxidative products of guanine". Nucleic Acids Symp Ser (Oxf). 48 (1): 171–2. doi:10.1093/nass/48.1.171. PMID 17150533.
- Ewing RM, Chu P, Elisma F, et al. (2007). "Large-scale mapping of human protein–protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
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