DNA polymerase ε and its roles in genome stability - PubMed (original) (raw)
Review
doi: 10.1002/iub.1276. Epub 2014 May 24.
Affiliations
- PMID: 24861832
- DOI: 10.1002/iub.1276
Free article
Review
DNA polymerase ε and its roles in genome stability
Erin E Henninger et al. IUBMB Life. 2014 May.
Free article
Abstract
DNA Polymerase Epsilon (Pol ε) is one of three DNA Polymerases (along with Pol δ and Pol α) required for nuclear DNA replication in eukaryotes. Pol ε is comprised of four subunits, the largest of which is encoded by the POLE gene and contains the catalytic polymerase and exonuclease activities. The 3'-5' exonuclease proofreading activity is able to correct DNA synthesis errors and helps protect against genome instability. Recent cancer genome sequencing efforts have shown that 3% of colorectal and 7% of endometrial cancers contain mutations within the exonuclease domain of POLE and are associated with significantly elevated levels of single nucleotide substitutions (15-500 per Mb) and microsatellite stability. POLE mutations have also been found in other tumor types, though at lower frequency, suggesting roles in tumorigenesis more broadly in different tissue types. In addition to its proofreading activity, Pol ε contributes to genome stability through multiple mechanisms that are discussed in this review.
Keywords: DNA polymerase; DNA replication; cancer; genome stability.
© 2014 International Union of Biochemistry and Molecular Biology.
Similar articles
- Evidence that errors made by DNA polymerase alpha are corrected by DNA polymerase delta.
Pavlov YI, Frahm C, Nick McElhinny SA, Niimi A, Suzuki M, Kunkel TA. Pavlov YI, et al. Curr Biol. 2006 Jan 24;16(2):202-7. doi: 10.1016/j.cub.2005.12.002. Curr Biol. 2006. PMID: 16431373 - Human Pol ε-dependent replication errors and the influence of mismatch repair on their correction.
Agbor AA, Göksenin AY, LeCompte KG, Hans SH, Pursell ZF. Agbor AA, et al. DNA Repair (Amst). 2013 Nov;12(11):954-63. doi: 10.1016/j.dnarep.2013.08.012. Epub 2013 Sep 17. DNA Repair (Amst). 2013. PMID: 24051051 Free PMC article. - Evidence for interplay among yeast replicative DNA polymerases alpha, delta and epsilon from studies of exonuclease and polymerase active site mutations.
Pavlov YI, Maki S, Maki H, Kunkel TA. Pavlov YI, et al. BMC Biol. 2004 May 26;2:11. doi: 10.1186/1741-7007-2-11. BMC Biol. 2004. PMID: 15163346 Free PMC article. - POLE proofreading defects: Contributions to mutagenesis and cancer.
Park VS, Pursell ZF. Park VS, et al. DNA Repair (Amst). 2019 Apr;76:50-59. doi: 10.1016/j.dnarep.2019.02.007. Epub 2019 Feb 16. DNA Repair (Amst). 2019. PMID: 30818169 Free PMC article. Review. - A panoply of errors: polymerase proofreading domain mutations in cancer.
Rayner E, van Gool IC, Palles C, Kearsey SE, Bosse T, Tomlinson I, Church DN. Rayner E, et al. Nat Rev Cancer. 2016 Feb;16(2):71-81. doi: 10.1038/nrc.2015.12. Nat Rev Cancer. 2016. PMID: 26822575 Review.
Cited by
- Polymerase-mediated ultramutagenesis in mice produces diverse cancers with high mutational load.
Li HD, Cuevas I, Zhang M, Lu C, Alam MM, Fu YX, You MJ, Akbay EA, Zhang H, Castrillon DH. Li HD, et al. J Clin Invest. 2018 Aug 31;128(9):4179-4191. doi: 10.1172/JCI122095. Epub 2018 Aug 20. J Clin Invest. 2018. PMID: 30124468 Free PMC article. - Reliable Pan-Cancer Microsatellite Instability Assessment by Using Targeted Next-Generation Sequencing Data.
Middha S, Zhang L, Nafa K, Jayakumaran G, Wong D, Kim HR, Sadowska J, Berger MF, Delair DF, Shia J, Stadler Z, Klimstra DS, Ladanyi M, Zehir A, Hechtman JF. Middha S, et al. JCO Precis Oncol. 2017;2017:PO.17.00084. doi: 10.1200/PO.17.00084. Epub 2017 Oct 3. JCO Precis Oncol. 2017. PMID: 30211344 Free PMC article. - Current status of the genetic susceptibility in attenuated adenomatous polyposis.
Lorca V, Garre P. Lorca V, et al. World J Gastrointest Oncol. 2019 Dec 15;11(12):1101-1114. doi: 10.4251/wjgo.v11.i12.1101. World J Gastrointest Oncol. 2019. PMID: 31908716 Free PMC article. Review. - Genome-scale CRISPR screen reveals neddylation to contribute to cisplatin resistance of testicular germ cell tumours.
Funke K, Einsfelder U, Hansen A, Arévalo L, Schneider S, Nettersheim D, Stein V, Schorle H. Funke K, et al. Br J Cancer. 2023 Jun;128(12):2270-2282. doi: 10.1038/s41416-023-02247-5. Epub 2023 Apr 6. Br J Cancer. 2023. PMID: 37024667 Free PMC article. - The dominant role of proofreading exonuclease activity of replicative polymerase ε in cellular tolerance to cytarabine (Ara-C).
Tsuda M, Terada K, Ooka M, Kobayashi K, Sasanuma H, Fujisawa R, Tsurimoto T, Yamamoto J, Iwai S, Kadoda K, Akagawa R, Huang SN, Pommier Y, Sale JE, Takeda S, Hirota K. Tsuda M, et al. Oncotarget. 2017 May 16;8(20):33457-33474. doi: 10.18632/oncotarget.16508. Oncotarget. 2017. PMID: 28380422 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous