DNA polymerase theta is an enzyme that in humans is encoded by the POLQgene.[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. PMID10395804.
↑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. PMID27264557.
↑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. PMID25275444.
↑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. PMID25642960.
↑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. PMID25642963.
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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. PMID14735462.
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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. PMID16520097.
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. PMID16603639.
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. PMID16824193.
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. PMID16835218.
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. PMID17150533.