{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:21:15Z","timestamp":1792102875485,"version":"4.4.0"},"reference-count":196,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T00:00:00Z","timestamp":1727395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kingdom of Saudi Arabia PhD scholarship"},{"name":"University of Galway College of Science and Engineering PhD scholarship"},{"name":"University of Galway Beckman Research Fund"},{"name":"School of Biological and Chemical Sciences at the University of Galway"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>DNA damage tolerance pathways that allow for the completion of replication following fork arrest are critical in maintaining genome stability during cell division. The main DNA damage tolerance pathways include strand switching, replication fork reversal and translesion synthesis (TLS). The TLS pathway is mediated by specialised DNA polymerases that can accommodate altered DNA structures during DNA synthesis, and are important in allowing replication to proceed after fork arrest, preventing fork collapse that can generate more deleterious double-strand breaks in the genome. TLS may occur directly at the fork, or at gaps remaining behind the fork, in the process of post-replication repair. Inactivating mutations in the human POLH gene encoding the Y-family DNA polymerase Pol \u03b7 causes the skin cancer-prone genetic disease xeroderma pigmentosum variant (XPV). Pol \u03b7 also contributes to chemoresistance during cancer treatment by bypassing DNA lesions induced by anti-cancer drugs including cisplatin. We review the current understanding of the canonical role of Pol \u03b7 in translesion synthesis following replication arrest, as well as a number of emerging non-canonical roles of the protein in other aspects of DNA metabolism.<\/jats:p>","DOI":"10.3390\/genes15101271","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T11:19:33Z","timestamp":1727435973000},"page":"1271","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Canonical and Non-Canonical Roles of Human DNA Polymerase \u03b7"],"prefix":"10.3390","volume":"15","author":[{"given":"Salma","family":"Bedaiwi","sequence":"first","affiliation":[{"name":"DNA Damage Response Laboratory, Centre for Chromosome Biology, School of Biological and Chemical Sciences, University of Galway, Galway H91W2TY, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8582-875X","authenticated-orcid":false,"given":"Anam","family":"Usmani","sequence":"additional","affiliation":[{"name":"DNA Damage Response Laboratory, Centre for Chromosome Biology, School of Biological and Chemical Sciences, University of Galway, Galway H91W2TY, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0342-9297","authenticated-orcid":false,"given":"Michael P.","family":"Carty","sequence":"additional","affiliation":[{"name":"DNA Damage Response Laboratory, Centre for Chromosome Biology, School of Biological and Chemical Sciences, University of Galway, Galway H91W2TY, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ler, A.I.L., and Carty, M.P. (2022). DNA damage tolerance pathways in human cells: A potential therapeutic target. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.822500"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Nickoloff, J.A., Jaiswal, A.S., Sharma, N., Williamson, E.A., Tran, M.T., Arris, D., Yang, M., and Hromas, R. (2023). Cellular Responses to Widespread DNA Replication Stress. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242316903"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/nrc2998","article-title":"DNA polymerases and cancer","volume":"11","author":"Lange","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1080\/10409238.2017.1291576","article-title":"Translesion DNA polymerases in eukaryotes: What makes them tick?","volume":"52","author":"Vaisman","year":"2017","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Sale, J. (2013). Translesion DNA Synthesis and Mutagenesis in Eukaryotes. Cold Spring Harb. Perspect. Biol., 5.","DOI":"10.1101\/cshperspect.a012708"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/nrm3289","article-title":"Y-family DNA polymerases and their role in tolerance of cellular DNA damage","volume":"13","author":"Sale","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2793","DOI":"10.1021\/bi500019s","article-title":"An Overview of Y-Family DNA Polymerases and a Case Study of Human DNA Polymerase \u03b7","volume":"53","author":"Yang","year":"2014","journal-title":"Biochemistry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1093\/nar\/gkad1054","article-title":"PRIMPOL ensures robust handoff between on-the-fly and post-replicative DNA lesion bypass","volume":"52","author":"Mellor","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.dnarep.2015.04.001","article-title":"DNA polymerases: Biology, diseases and biomedical applications","volume":"29","author":"Woodgate","year":"2015","journal-title":"DNA Repair"},{"key":"ref_10","first-page":"123","article-title":"Insights into the role of DNA polymerase eta in maintaining genome stability and its implications for cancer therapy","volume":"21","author":"Anand","year":"2023","journal-title":"Mol. Cancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1146\/annurev.biochem.74.082803.133250","article-title":"Eukaryotic translesion synthesis DNA polymerases: Specificity of structure and function","volume":"74","author":"Prakash","year":"2005","journal-title":"Ann. Rev. Biochem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3875","DOI":"10.1093\/nar\/gki702","article-title":"Origin and evolution of the archaeo-eukaryotic primase superfamily and related palm-domain proteins: Structural insights and new members","volume":"33","author":"Iyer","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1038\/embor.2013.159","article-title":"hPrimpol1\/CCDC111 is a human DNA primase-polymerase required for the maintenance of genome integrity","volume":"14","author":"Wan","year":"2013","journal-title":"EMBO Rep."},{"key":"ref_14","first-page":"5086","article-title":"Repriming of DNA synthesis at stalled replication forks by DNA polymerase \u03b7","volume":"41","author":"Mouron","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.molcel.2013.09.025","article-title":"PrimPol, an archaic primase\/polymerase operating in human cells","volume":"52","author":"Reyes","year":"2013","journal-title":"Mol. Cell."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.molcel.2013.10.035","article-title":"PrimPol bypasses UV photoproducts during eukaryotic chromosomal DNA replication","volume":"52","author":"Bianchi","year":"2013","journal-title":"Mol. Cell."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1111\/1523-1747.ep12538913","article-title":"Xeroderma pigmentosum: Variants with normal DNA repair and normal sensitivity to UV light","volume":"58","author":"Cleaver","year":"1972","journal-title":"J. Investig. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1038\/21447","article-title":"The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase \u03b7","volume":"399","author":"Masutani","year":"1999","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1126\/science.285.5425.263","article-title":"hRAD30 mutations in the variant form of xeroderma pigmentosum","volume":"285","author":"Johnson","year":"1999","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2830","DOI":"10.1093\/nar\/gkp103","article-title":"The efficiency and fidelity of 8-oxo-guanine bypass by DNA polymerases delta and \u03b7","volume":"37","author":"McCulloch","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"503498","DOI":"10.1016\/j.mrgentox.2022.503498","article-title":"DNA polymerase \u03b7 protects human cells against DNA damage induced by the tumor chemotherapeutic temozolomide","volume":"878","author":"Latancia","year":"2022","journal-title":"Mut. Res.-Genetic Toxicol. Environ. Mutagen."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6469","DOI":"10.1158\/0008-5472.CAN-04-1328","article-title":"The role of DNA polymerase eta in translesion synthesis past platinum-DNA adducts in human fibroblasts","volume":"64","author":"Bassett","year":"2004","journal-title":"Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1126\/science.1148242","article-title":"Bypass of DNA lesions generated during anticancer treatment with cisplatin by DNA polymerase eta","volume":"318","author":"Alt","year":"2007","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7269","DOI":"10.1073\/pnas.1202681109","article-title":"Structural basis of human DNA polymerase \u03b7-mediated chemoresistance to cisplatin","volume":"109","author":"Zhao","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Sokol, A.M., Cruet-Hennequart, S., Pasero, P., and Carty, M.P. (2013). DNA polymerase \u03b7 modulates replication fork progression and DNA damage responses in platinum-treated human cells. Sci. Rep., 3.","DOI":"10.1038\/srep03277"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9799","DOI":"10.1158\/0008-5472.CAN-05-1095","article-title":"A role for polymerase eta in the cellular tolerance to cisplatin-induced damage","volume":"65","author":"Albertella","year":"2005","journal-title":"Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.dnarep.2007.12.012","article-title":"Enhanced DNA-PK-mediated RPA2 hyperphosphorylation in DNA polymerase \u03b7-deficient human cells treated with cisplatin and oxaliplatin","volume":"7","author":"Glynn","year":"2008","journal-title":"DNA Repair"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3043","DOI":"10.4161\/cc.8.18.9624","article-title":"Characterization of the effects of cisplatin and carboplatin on cell cycle progression and DNA damage response activation in DNA polymerase \u03b7-deficient human cells","volume":"8","author":"Villalan","year":"2009","journal-title":"Cell Cycle"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1158\/1078-0432.CCR-08-1227","article-title":"Polymerase eta mRNA expression predicts survival of non-small cell lung cancer patients treated with platinum-based chemotherapy","volume":"15","author":"Ceppi","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4411","DOI":"10.1073\/pnas.1421365112","article-title":"Enhanced expression of DNA polymerase eta contributes to cisplatin resistance of ovarian cancer stem cells","volume":"112","author":"Srivastava","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4106","DOI":"10.1002\/jcp.30155","article-title":"DNA polymerase \u03b7: A potential pharmacological target for cancer therapy","volume":"236","author":"Saha","year":"2021","journal-title":"J. Cell Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"115044","DOI":"10.1016\/j.ejmech.2022.115044","article-title":"Computer-aided identification, synthesis, and biological evaluation of DNA polymerase \u03b7 inhibitors for the treatment of cancer","volume":"248","author":"Nigro","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1007\/s00294-018-0918-5","article-title":"Multifaceted activities of DNA polymerase \u03b7: Beyond translesion DNA synthesis","volume":"65","author":"Acharya","year":"2019","journal-title":"Curr. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3608","DOI":"10.1016\/j.molcel.2023.07.008","article-title":"Freedom to err: The expanding cellular functions of translesion DNA polymerases","volume":"8","author":"Paniagua","year":"2023","journal-title":"Mol. Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3344","DOI":"10.1128\/MCB.00115-09","article-title":"Human DNA Polymerase \u03b7 is required for common fragile site stability during unperturbed DNA replication","volume":"29","author":"Rey","year":"2009","journal-title":"Mol. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1083\/jcb.201207066","article-title":"DNA synthesis by Pol \u03b7 promotes fragile site stability by preventing under-replicated DNA in mitosis","volume":"201","author":"Bergoglio","year":"2013","journal-title":"J. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6549","DOI":"10.1158\/0008-5472.CAN-17-3931","article-title":"DNA polymerase \u03b7 prevents tumor cell-cycle arrest and cell death during recovery from replication stress","volume":"78","author":"Barnes","year":"2018","journal-title":"Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e2106477118","DOI":"10.1073\/pnas.2106477118","article-title":"Translesion polymerase \u03b7 both facilitates DNA replication and promotes increased human genetic variation at common fragile sites","volume":"118","author":"Twayana","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/88740","article-title":"DNA polymerase \u03b7 is an A-T mutator in somatic hypermutation of immunoglobulin variable genes","volume":"2","author":"Zeng","year":"2001","journal-title":"Nat. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1084\/jem.20042066","article-title":"MSH2\u2013MSH6 stimulates DNA polymerase \u03b7, suggesting a role for A:T mutations in antibody genes","volume":"201","author":"Wilson","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6353","DOI":"10.4049\/jimmunol.0900177","article-title":"A backup role of DNA polymerase kappa in Ig gene hypermutation only takes place in the complete absence of DNA polymerase \u03b7","volume":"182","author":"Faili","year":"2009","journal-title":"J. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3747","DOI":"10.1074\/jbc.M115.706226","article-title":"Mechanism of Ribonucleotide Incorporation by Human DNA Polymerase \u03b7","volume":"291","author":"Su","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_43","first-page":"2600","article-title":"Ribonucleotide incorporation by human DNA polymerase \u03b7 impacts translesion synthesis and RNase H2 activity","volume":"45","author":"Mentegari","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"14203","DOI":"10.1074\/jbc.RA120.013812","article-title":"Replication protein A binds RNA and promotes R-loop formation","volume":"295","author":"Mazina","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Chang, C., Luo, C.L., Eleraky, S., Lin, A., Zhou, G., and Gao, Y. (2023). Primer terminal ribonucleotide alters the active site dynamics of DNA polymerase \u03b7 and reduces DNA synthesis fidelity. J. Biol. Chem., 299.","DOI":"10.1016\/j.jbc.2023.102938"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"18044","DOI":"10.1074\/jbc.M117.809723","article-title":"Human DNA polymerase \u03b7 accommodates RNA for strand extension","volume":"292","author":"Su","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6073","DOI":"10.1074\/jbc.RA119.007925","article-title":"Human DNA polymerase \u03b7 has reverse transcriptase activity in cellular environments","volume":"294","author":"Su","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Chakraborty, A., Tapryal, N., Islam, A., Sarker, A.H., Manohar, K., Mitra, J., Hegde, M.L., and Hazra, T. (2023). Human DNA polymerase \u03b7 promotes RNA-templated error-free repair of DNA double-strand breaks. J. Biol. Chem., 299.","DOI":"10.1016\/j.jbc.2023.102991"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.molcel.2005.10.001","article-title":"Human DNA polymerase \u03b7 promotes DNA synthesis from strand invasion intermediates of homologous recombination","volume":"20","author":"McIlwraith","year":"2005","journal-title":"Mol. Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.dnarep.2013.05.001","article-title":"Role of PCNA and TLS polymerases in D-loop extension duringhomologous recombination in humans","volume":"12","author":"Sebesta","year":"2013","journal-title":"DNA Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.celrep.2014.01.009","article-title":"Breast Cancer Proteins PALB2 and BRCA2 Stimulate Polymerase h in Recombination-Associated DNA Synthesis at Blocked Replication Forks","volume":"6","author":"Buisson","year":"2014","journal-title":"Cell Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"13096","DOI":"10.1093\/nar\/gku1030","article-title":"Polymerase \u03b7 suppresses telomere defects induced by DNA damaging agents","volume":"42","author":"Liu","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1016\/j.celrep.2016.10.048","article-title":"Proteomic Profiling Reveals a Specific Role for Translesion DNA Polymerase \u03b7 in the Alternative Lengthening of Telomeres","volume":"17","author":"Bournique","year":"2016","journal-title":"Cell Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1038\/nature09196","article-title":"Structure and mechanism of human DNA polymerase \u03b7","volume":"465","author":"Biertumpfel","year":"2010","journal-title":"Nature"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/nsmb.2295","article-title":"Structural basis for cisplatin DNA damage tolerance by human polymerase \u03b7 during cancer chemotherapy","volume":"19","author":"Ummat","year":"2012","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/nature11181","article-title":"Watching DNA polymerase eta make a phosphodiester bond","volume":"487","author":"Nakamura","year":"2012","journal-title":"Nature"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.jmb.2011.11.038","article-title":"Human DNA Polymerase \u03b7 Is Pre-Aligned for dNTP Binding and Catalysis","volume":"415","author":"Ummat","year":"2012","journal-title":"J. Mol. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1126\/science.aad9633","article-title":"Capture of a third Mg 2+ is essential for catalyzing DNA synthesis","volume":"352","author":"Gao","year":"2016","journal-title":"Science"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2346","DOI":"10.1038\/s41467-022-30005-3","article-title":"In crystallo observation of three metal ion promoted DNA polymerase misincorporation","volume":"13","author":"Chang","year":"2022","journal-title":"Nat. Comm."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/sj.embor.7400901","article-title":"Structure of the ubiquitin-binding zinc finger domain of human DNA Y-polymerase eta","volume":"8","author":"Bomar","year":"2007","journal-title":"EMBO Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5506","DOI":"10.1021\/bi300566z","article-title":"NMR structure and dynamics of the C-terminal domain from human Rev1 and its complex with Rev1 interacting region of DNA polymerase eta","volume":"51","author":"Pozhidaeva","year":"2012","journal-title":"Biochemistry"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"205","DOI":"10.3390\/dna2040015","article-title":"Contributing Factors for Mutagenic DNA Lesion Bypass by DNA Polymerase H (pol\u03b7)","volume":"2","author":"Jung","year":"2022","journal-title":"DNA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"17724","DOI":"10.1073\/pnas.0809844105","article-title":"Roles of PCNA-binding and ubiquitin-binding domains in human DNA polymerase eta in translesion DNA synthesis","volume":"105","author":"Acharya","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"10401","DOI":"10.1073\/pnas.1005492107","article-title":"DNA polymerase eta lacking the ubiquitin-binding domain promotes replicative lesion bypass in humans cells","volume":"107","author":"Acharya","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Hendel, A., Krijger, P.H., Diamant, N., Goren, Z., Langerak, P., Kim, J., Reissner, T., Lee, K.Y., Geacintov, N.E., and Carell, T. (2011). PCNA ubiquitination is important, but not essential for translesion DNA synthesis in mammalian cells. PLoS Genet., 7.","DOI":"10.1371\/journal.pgen.1002262"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jbiotec.2023.12.001","article-title":"Exploring RAD18-dependent replication of damaged DNA and discontinuities: A collection of advanced tools","volume":"380","author":"Morocz","year":"2024","journal-title":"J. Biotechnol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/S1097-2765(04)00259-X","article-title":"Interaction of human DNA polymerase eta with monoubiquitinated PCNA: A possible mechanism for the polymerase switch in response to DNA damage","volume":"14","author":"Kannouche","year":"2004","journal-title":"Mol. Cell"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.molcel.2009.12.039","article-title":"Regulation of translesion synthesis DNA polymerase eta by monoubiquitination","volume":"37","author":"Bienko","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3886","DOI":"10.1038\/sj.emboj.7600383","article-title":"Rad18 guides pol eta to replication stalling sites through physical interaction and PCNA monoubiquitination","volume":"23","author":"Watanabe","year":"2004","journal-title":"EMBO J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3079","DOI":"10.1093\/nar\/gkt016","article-title":"A non-catalytic role of DNA polymerase \u03b7 in recruiting Rad18 and promoting PCNA monoubiquitination at stalled replication forks","volume":"41","author":"Durando","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4560","DOI":"10.1093\/nar\/gky220","article-title":"RNA-splicing factor SART3 regulates translesion DNA synthesis","volume":"46","author":"Huang","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"13558","DOI":"10.1073\/pnas.1306534110","article-title":"BRCA1 promotes the ubiquitination of PCNA and recruitment of translesion polymerases in response to replication blockade","volume":"110","author":"Tian","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"803","DOI":"10.4161\/cc.23755","article-title":"Recruitment of DNA polymerase eta by FANCD2 in the early response to DNA damage","volume":"12","author":"Fu","year":"2013","journal-title":"Cell Cycle"},{"key":"ref_75","first-page":"5201","article-title":"Regulation of DNA polymerase \u03b7 activity by the ubiquitin-proteasome system","volume":"36","author":"Edmunds","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"8250","DOI":"10.1093\/nar\/gkw563","article-title":"PCNA tool belts and polymerase bridges form during translesion synthesis","volume":"44","author":"Boehm","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5437","DOI":"10.1038\/ncomms6437","article-title":"Identification of novel DNA-damage tolerance genes reveals regulation of translesion DNA synthesis by nucleophosmin","volume":"5","author":"Ziv","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"42312","DOI":"10.1074\/jbc.M112.410332","article-title":"Enhancement of Human DNA Polymerase \u03b7 Activity and Fidelity Is Dependent Upon a Bipartite Interaction with the Werner Syndrome Protein","volume":"287","author":"Maddukuri","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"16578","DOI":"10.1073\/pnas.0808589105","article-title":"Human DNA polymerase eta activity and translocation is regulated by phosphorylation","volume":"105","author":"Chen","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"9441","DOI":"10.1093\/nar\/gkx619","article-title":"Phosphorylation regulates human pol\u03b7 stability and damage bypass throughout the cell cycle","volume":"45","author":"Bertoletti","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1083\/jcb.201008076","article-title":"ATR-mediated phosphorylation of DNA polymerase eta is needed for efficient recovery from UV damage","volume":"192","author":"Gohler","year":"2011","journal-title":"J. Cell Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.isci.2018.07.009","article-title":"Phosphorylation alters the properties of Pol \u03b7: Implications for translesion synthesis","volume":"6","author":"Peddu","year":"2018","journal-title":"iScience"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.1128\/MCB.05808-11","article-title":"Pirh2 E3 ubiquitin ligase monoubiquitinates DNA polymerase \u03b7 to suppress translesion DNA synthesis","volume":"31","author":"Jung","year":"2011","journal-title":"Mol. Cell Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"8350","DOI":"10.1074\/jbc.RA120.013780","article-title":"Multisite SUMOylation restrains DNA polymerase \u03b7 interactions with DNA damage sites","volume":"295","author":"Smedegaard","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.dnarep.2011.10.017","article-title":"DNA polymerase \u03b7 is targeted by Mdm2 for polyubiquitination and proteasomal degradation in response to ultraviolet irradiation","volume":"11","author":"Jung","year":"2012","journal-title":"DNA Repair"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.dnarep.2015.02.011","article-title":"Regulation of translesion DNA synthesis: Post-translational modification of lysine residues in key proteins","volume":"29","author":"McIntyre","year":"2015","journal-title":"DNA Repair"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"13326","DOI":"10.1038\/ncomms13326","article-title":"Rad18-dependent SUMOylation of human specialized DNA polymerase \u03b7 is required to prevent under-replicated DNA","volume":"7","author":"Despras","year":"2016","journal-title":"Nature Comm."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.molcel.2006.03.022","article-title":"p53 and p21 regulate error-prone DNA repair to yield a lower mutation load","volume":"22","author":"Avkin","year":"2006","journal-title":"Mol. Cell"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1093\/nar\/gkw1196","article-title":"Predominant role of DNA polymerase eta and p53-dependent translesion synthesis in the survival of ultraviolet-irradiated human cells","volume":"45","author":"Lerner","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Wendel, S.O., Snow, J.A., Bastian, T., Brown, L., Hernandez, C., Burghardt, E., Kahn, A., Murthy, V., Neill, D., and Smith, Z.C. (2021). High Risk \u03b1-HPV E6 Impairs Translesion Synthesis by Blocking POL\u03b7 Induction. Cancers, 13.","DOI":"10.3390\/cancers13010028"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1002\/gcc.1186","article-title":"DNA polymerase eta undergoes alternative splicing, protects against UV sensitivity and apoptosis, and suppresses Mre11-dependent recombination","volume":"32","author":"Thakur","year":"2001","journal-title":"Genes Chrom. Cancer"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3714","DOI":"10.1158\/0008-5472.CAN-18-3928","article-title":"PolH Transcript with a Short 3\u2019 UTR Enhances PolH Expression and Mediates Cisplatin Resistance","volume":"79","author":"Zhang","year":"2019","journal-title":"Cancer Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1111\/cas.16150","article-title":"Long noncoding RNA TUG1 promotes cisplatin resistance in ovarian cancer via upregulation of DNA polymerase \u03b7","volume":"115","author":"Sonobe","year":"2024","journal-title":"Cancer Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"728","DOI":"10.4161\/cc.9.4.10727","article-title":"Multiple two-polymerase mechanisms in mammalian translesion DNA synthesis","volume":"9","author":"Livneh","year":"2010","journal-title":"Cell Cycle"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3100","DOI":"10.1093\/emboj\/19.12.3100","article-title":"Mechanisms of accurate translesion synthesis by human DNA polymerase eta","volume":"19","author":"Masutani","year":"2000","journal-title":"EMBO J."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/78169","article-title":"Efficient and accurate replication of 7,8-dihydro-8-oxoguanine by DNA polymerase \u03b7","volume":"25","author":"Haracska","year":"2000","journal-title":"Nat. Genetics"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"16867","DOI":"10.1074\/jbc.M114.551820","article-title":"Kinetics, structure, and mechanism of 8-Oxo-7,8-dihydro-2\u2019-deoxyguanosine bypass by human DNA polymerase \u03b7","volume":"289","author":"Patra","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"24304","DOI":"10.1074\/jbc.M116.755462","article-title":"Mechanisms of Insertion of dCTP and dTTP Opposite the DNA Lesion O6-Methyl-2\u2019-deoxyguanosine by Human DNA Polymerase \u03b7","volume":"291","author":"Patra","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4575","DOI":"10.1021\/bi000130k","article-title":"Efficient translesion replication past oxaliplatin and cisplatin GpG adducts by human DNA polymerase eta","volume":"39","author":"Vaisman","year":"2000","journal-title":"Biochemistry"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"4295","DOI":"10.1093\/nar\/gkae102","article-title":"Novel insights into the role of translesion synthesis polymerase in DNA incorporation and bypass of 5-fluorouracil in colorectal cancer","volume":"52","author":"Averill","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"4717","DOI":"10.1093\/nar\/28.23.4717","article-title":"Error-prone lesion bypass by human DNA polymerase \u03b7","volume":"28","author":"Zhang","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1021\/acs.chemrestox.6b00221","article-title":"Translesion Synthesis of the N(2)-2\u2019-Deoxyguanosine Adduct of the Dietary Mutagen IQ in Human Cells: Error-Free Replication by DNA Polymerase \u03ba and Mutagenic Bypass by DNA Polymerases \u03b7, \u03b6, and Rev1","volume":"29","author":"Bose","year":"2016","journal-title":"Chem. Res. Toxicol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"3984","DOI":"10.1093\/nar\/gkh710","article-title":"Role of DNA polymerase \u03b7 in the bypass of abasic sites in yeast cells","volume":"32","author":"Zhao","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jmb.2010.09.015","article-title":"Translesion synthesis across abasic lesions by human B-family and Y-family DNA polymerases \u03b1, \u03b2, \u03b7, \u03b9, \u03ba and REV1","volume":"404","author":"Choi","year":"2010","journal-title":"J. Mol. Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"8028","DOI":"10.1074\/jbc.M115.637561","article-title":"Structural and kinetic analysis of nucleoside triphosphate incorporation opposite an abasic site by human translesion DNA polymerase \u03b7","volume":"290","author":"Patra","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"3558","DOI":"10.1128\/MCB.21.10.3558-3563.2001","article-title":"Role of DNA polymerase eta in the bypass of a (6-4) TT photoproduct","volume":"21","author":"Johnson","year":"2001","journal-title":"Mol. Cell Biol."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Ling, J.A., Frevert, Z., and Washington, M.T. (2022). Recent advances in understanding the structures of translesion synthesis DNA polymerases. Genes, 13.","DOI":"10.3390\/genes13050915"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1073\/pnas.022473899","article-title":"Molecular analysis of mutations in DNA polymerase \u03b7 in xeroderma pigmentosum-variant patients","volume":"99","author":"Broughton","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1038\/s41467-023-38311-0","article-title":"Genomic mutation landscape of skin cancers from DNA repair-deficient xeroderma pigmentosum patients","volume":"14","author":"Yurchenko","year":"2023","journal-title":"Nature Comm."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1093\/carcin\/bgad030","article-title":"Mutational signatures and increased retrotransposon insertions in xeroderma pigmentosum variant skin tumors","volume":"44","author":"Corradi","year":"2023","journal-title":"Carcinogenesis"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"111840","DOI":"10.1016\/j.mrfmmm.2023.111840","article-title":"The accurate bypass of pyrimidine dimers by DNA polymerase \u03b7 contributes to ultraviolet-induced mutagenesis","volume":"828","author":"Menck","year":"2024","journal-title":"Mut. Res. Fund. Mol. Mech. Mutagen."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"9133","DOI":"10.1073\/pnas.1405739111","article-title":"Structural and mechanistic studies of polymerase \u03b7 bypass of phenanthriplatin DNA damage","volume":"111","author":"Gregory","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Ma, X., Taniguchi, T., Xu, Z., Feng, J., Cheng, S., Zhang, L., Lo, A., Zhang, M., Liu, Y., and Li, L. (2022). DNA polymerase \u03b7 promotes nonhomologous end joining upon etoposide exposure dependent on the scaffolding protein Kap1. J. Biol. Chem., 298.","DOI":"10.1016\/j.jbc.2022.101861"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"7857","DOI":"10.1021\/acs.chemrev.7b00046","article-title":"Eukaryotic Translesion DNA Synthesis on the Leading and Lagging Strands: Unique Detours around the Same Obstacle","volume":"117","author":"Hedglin","year":"2017","journal-title":"Chem. Rev."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e2216055120","DOI":"10.1073\/pnas.2216055120","article-title":"Mammalian life depends on two distinct pathways of DNA damage tolerance","volume":"120","author":"Buoninfante","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.molcel.2021.01.012","article-title":"To skip or not to skip: Choosing repriming to tolerate DNA damage","volume":"81","author":"Quinet","year":"2021","journal-title":"Mol. Cell"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"4026","DOI":"10.1016\/j.molcel.2021.09.013","article-title":"Temporally distinct post-replicative repair mechanisms fill PRIMPOL-dependent ssDNA gaps in human cells","volume":"81","author":"Tirman","year":"2021","journal-title":"Mol. Cell"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/nature00991","article-title":"RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO","volume":"419","author":"Hoege","year":"2002","journal-title":"Nature"},{"key":"ref_119","first-page":"951","article-title":"DNA polymerase \u03b7: Structural insights and biological significance","volume":"9","author":"Freudenthal","year":"2010","journal-title":"DNA Repair"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1146\/annurev-biophys-060414-033841","article-title":"Regulation of Rad6\/Rad18 Activity During DNA Damage Tolerance","volume":"44","author":"Hedglin","year":"2015","journal-title":"Annu. Rev. Biophys."},{"key":"ref_121","first-page":"1423","article-title":"The role of DNA polymerase \u03b7 in genome stability and its implications in cancer therapy","volume":"109","author":"Masuda","year":"2018","journal-title":"Cancer Sci."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1080\/10409238.2017.1380597","article-title":"Functions of SMARCAL1, ZRANB3, and HLTF in maintaining genome stability","volume":"52","author":"Poole","year":"2017","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_123","first-page":"10277","article-title":"Human HLTF mediates post-replication repair by its HIRAN domain-dependent replication fork remodelling","volume":"43","author":"Achar","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.molcel.2012.05.024","article-title":"Polyubiquitinated PCNA recruits the ZRANB3 translocase to maintain genomic integrity after replication stress","volume":"47","author":"Ciccia","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1016\/j.molcel.2020.04.031","article-title":"HLTF promotes fork reversal, limiting replication stress resistance and preventing multiple mechanisms of unrestrained DNA synthesis","volume":"78","author":"Bai","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"3033","DOI":"10.1093\/nar\/gkab101","article-title":"Mechanisms of damage tolerance and repair during DNA replication","volume":"49","author":"Ashour","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_127","unstructured":"Lemacon, D., and Boudsocq, F. (2017). DNA polymerase \u03b7 in replication and repair: A detailed review. Int. J. Mol. Sci., 18."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.cell.2011.03.041","article-title":"Double-strand break repair-independent role for BRCA2 in blocking stalled replication fork degradation by MRE11","volume":"145","author":"Schlacher","year":"2011","journal-title":"Cell"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.molcel.2017.09.036","article-title":"Restoration of replication fork stability in BRCA1- and BRCA2-deficient cells by inactivation of SNF2-family fork remodelers","volume":"68","author":"Taglialatela","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1101\/gad.336446.120","article-title":"Distinct roles of BRCA2 in replication fork protection in response to hydroxyurea and DNA interstrand cross-links","volume":"34","author":"Rickman","year":"2020","journal-title":"Genes Dev."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/s41467-021-27872-7","article-title":"BRCA1 deficiency specific base substitution mutagenesis is dependent on translesion synthesis and regulated by 53BP1","volume":"3","author":"Chen","year":"2022","journal-title":"Nat. Comm."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"5717","DOI":"10.1093\/nar\/gkw280","article-title":"Translesion synthesis mechanisms depend on the nature of DNA damage in UV-irradiated human cells","volume":"44","author":"Quinet","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"E6624","DOI":"10.1073\/pnas.1508543112","article-title":"Rad51 recombinase prevents Mre11 nuclease-dependent degradation and excessive PrimPol-mediated elongation of nascent DNA after UV irradiation","volume":"112","author":"Vallerga","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"9909","DOI":"10.1093\/nar\/gkac746","article-title":"Changes in the architecture and abundance of replication intermediates delineate the chronology of DNA damage tolerance pathways at UV-stalled replication forks in human cells","volume":"50","author":"Benureau","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/s41594-020-0418-4","article-title":"Reconstitution of translesion synthesis reveals a mechanism of eukaryotic DNA replication restart","volume":"27","author":"Guilliam","year":"2020","journal-title":"Nature Struct. Mol. Biol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"eaaz7808","DOI":"10.1126\/sciadv.aaz7808","article-title":"Inhibition of the translesion synthesis polymerase REV1 exploits replication gaps as a cancer vulnerability","volume":"6","author":"Nayak","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Bellani, M.A., Shaik, A., Majumdar, I., Ling, C., and Seidman, M.M. (2023). The response of the replication apparatus to leading template strand blocks. Cells, 12.","DOI":"10.3390\/cells12222607"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.molcel.2005.11.015","article-title":"Multiple mechanisms control chromosome integrity after replication fork uncoupling and restart at irreparable UV lesions","volume":"21","author":"Lopes","year":"2006","journal-title":"Mol. Cell"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1080\/15384101.2016.1191711","article-title":"Repriming by PrimPol is critical for DNA replication restart downstream of lesions and chain-terminating nucleosides","volume":"15","author":"Kobayashi","year":"2016","journal-title":"Cell Cycle"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"15222","DOI":"10.1038\/ncomms15222","article-title":"Molecular basis for PrimPol recruitment to replication forks by RPA","volume":"8","author":"Guilliam","year":"2017","journal-title":"Nature Comm."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"e960754","DOI":"10.4161\/23723548.2014.960754","article-title":"PrimPol\u2014A new polymerase on the block","volume":"1","author":"Rudd","year":"2014","journal-title":"Mol. Cell Oncol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"102947","DOI":"10.1016\/j.dnarep.2020.102947","article-title":"Mechanisms of direct replication restart at stressed replisomes","volume":"95","author":"Conti","year":"2020","journal-title":"DNA Repair"},{"key":"ref_143","unstructured":"Piberger, H., and Jantsch, M. (2020). Insights into the mechanisms of DNA polymerase \u03b7 during DNA damage repair. Int. J. Mol. Sci., 21."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"D\u00edaz-Talavera, A., Montero-Conde, C., Leandro-Garc\u00eda, L.J., and Robledo, M. (2022). PrimPol: A breakthrough among DNA replication enzymes and a potential new target for cancer therapy. Biomolecules, 12.","DOI":"10.3390\/biom12020248"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"7049","DOI":"10.1093\/nar\/gkr420","article-title":"UV stalled replication forks restart by re-priming in human fibroblasts","volume":"39","author":"Elvers","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"3881","DOI":"10.1093\/emboj\/cdf363","article-title":"Lesion bypass in yeast cells: Pol \u03b7 participates in a multi-DNA polymerase process","volume":"21","author":"Bresson","year":"2002","journal-title":"EMBO J."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1093\/nar\/gkr596","article-title":"DNA damage bypass operates in the S and G2 phases of the cell cycle and exhibits differential mutagenicity","volume":"40","author":"Diamant","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.mrgentox.2018.02.004","article-title":"Filling gaps in translesion DNA synthesis in human cells","volume":"836","author":"Quinet","year":"2018","journal-title":"Mutat. Res. Genet. Toxicol. Environ. Mutagen."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1016\/j.cell.2019.01.023","article-title":"Error-prone replication through UV lesions by DNA polymerase \u03b8 protects against skin cancers","volume":"176","author":"Yoon","year":"2019","journal-title":"Cell"},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Bell\u00ed, G., Colomina, N., Castells-Roca, L., and Lorite, N.P. (2022). Post-translational modifications of PCNA: Guiding for the best DNA damage tolerance choice. J. Fungi, 8.","DOI":"10.3390\/jof8060621"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"e478s","DOI":"10.6061\/clinics\/2018\/e478s","article-title":"DNA repair pathways and cisplatin resistance: An intimate relationship","volume":"73","author":"Silva","year":"2018","journal-title":"Clinics"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1007\/BF00272988","article-title":"DNA polymerase \u03b1 inhibition by aphidicolin induces gaps and breaks at common fragile sites in human chromosomes","volume":"67","author":"Glover","year":"1984","journal-title":"Hum. Genet."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Lerner, L.K., and Sale, J.E. (2019). Replication of G-Quadruplex DNA. Genes, 10.","DOI":"10.3390\/genes10020095"},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Li, Z., and Wu, X. (2020). Common fragile sites: Protection and repair. Cell Biosci., 18.","DOI":"10.1186\/s13578-020-00392-5"},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Maffia, A., Ranise, C., and Sabbioneda, S. (2020). From R-loops to G-quadruplexes: Emerging new threats for the replication fork. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041506"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"3218","DOI":"10.1021\/acs.biochem.5b00060","article-title":"Evidence for the Kinetic Partitioning of Polymerase Activity on G-Quadruplex DNA","volume":"54","author":"Eddy","year":"2015","journal-title":"Biochemistry"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.dnarep.2017.05.006","article-title":"DNA polymerases eta and kappa exchange with the polymerase \u03b4 holoenzyme to complete common fragile site synthesis","volume":"57","author":"Barnes","year":"2017","journal-title":"DNA Repair"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1002\/mc.20509","article-title":"Role of TLS DNA polymerases \u03b7 and kappa in processing naturally occurring structured DNA in human cells","volume":"48","author":"Rey","year":"2009","journal-title":"Mol. Carcinog."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Tsao, W.-C., and Eckert, K.A. (2018). Detours to Replication: Functions of Specialized DNA Polymerases during Oncogene-induced Replication Stress. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19103255"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"jcs212183","DOI":"10.1242\/jcs.212183","article-title":"Pol\u03b7, a Y-family translesion synthesis polymerase, promotes cellular tolerance of Myc-induced replication stress","volume":"131","author":"Kurashima","year":"2018","journal-title":"J. Cell Sci."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"100501","DOI":"10.1016\/j.crmeth.2023.100501","article-title":"Detection of endogenous translesion DNA synthesis in single mammalian cells","volume":"3","author":"Egger","year":"2023","journal-title":"Cell Rep. Meth."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1074\/mcp.M115.052167","article-title":"The functions of serine 687 phosphorylation of human DNA polymerase \u03b7 in UV damage tolerance","volume":"15","author":"Dai","year":"2016","journal-title":"Mol. Cell. Proteomics"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1038\/88732","article-title":"Somatic mutation hotspots correlate with DNA polymerase \u03b7 error spectrum","volume":"2","author":"Rogozin","year":"2001","journal-title":"Nature Immunol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"9954","DOI":"10.1073\/pnas.152126799","article-title":"Correlation of somatic hypermutation specificity and A-T base pair substitution errors by DNA polymerase eta during copying of a mouse immunoglobulin kappa light chain transgene","volume":"99","author":"Pavlov","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1084\/jem.20050292","article-title":"Contribution of DNA polymerase \u03b7 to immunoglobulin gene hypermutation in the mouse","volume":"201","author":"Delbos","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1084\/jem.20062131","article-title":"DNA polymerase \u03b7 is the sole contributor of A\/T modifications during immunoglobulin gene hypermutation in the mouse","volume":"204","author":"Delbos","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1084\/jem.20070902","article-title":"A\/T mutagenesis in hypermutated immunoglobulin genes strongly depends on PCNAK164 modification","volume":"204","author":"Langerak","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"16248","DOI":"10.1073\/pnas.0808182105","article-title":"Ubiquitylated PCNA plays a role in somatic hypermutation and class-switch recombination and is required for meiotic progression","volume":"105","author":"Roa","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/j.dnarep.2011.08.005","article-title":"PCNA ubiquitination-independent activation of polymerase \u03b7 during somatic hypermutation and DNA damage tolerance","volume":"10","author":"Krijger","year":"2011","journal-title":"DNA Repair"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"8146","DOI":"10.1073\/pnas.1303126110","article-title":"Mechanism of somatic hypermutation at the WA motif by human DNA polymerase \u03b7","volume":"110","author":"Zhao","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Lerner, L.K., Nguyen, T.V., Castro, L.P., Vilar, J.B., Munford, V., LeGuillou, M., Mohammad, M.M., Verg\u00e9, V., Rosselli, F., and Menck, C.F.M. (2020). Large deletions in immunoglobulin genes are associated with a sustained absence of DNA Polymerase \u03b7. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-58180-7"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1038\/s41586-022-05072-7","article-title":"Diverse mutational landscapes in human lymphocytes","volume":"608","author":"Machado","year":"2022","journal-title":"Nature"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1080\/15384101.2017.1404208","article-title":"DNA polymerase \u03b7 mutational signatures are found in a variety of different types of cancer","volume":"17","author":"Rogozin","year":"2018","journal-title":"Cell Cycle"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"13055","DOI":"10.1038\/s41598-017-12915-1","article-title":"Translesion synthesis DNA polymerase \u03b7 exhibits a specific RNA extension activity and a transcription-associated function","volume":"7","author":"Gali","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"16197","DOI":"10.1021\/jacs.1c07374","article-title":"DNA Polymerase \u03b7 Promotes the Transcriptional Bypass of N2\u2013Alkyl-2\u2032-deoxyguanosine Adducts in Human Cells","volume":"143","author":"Tan","year":"2021","journal-title":"J. Am. Chem. Soc."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"221","DOI":"10.3390\/dna2040016","article-title":"Size- and Stereochemistry-Dependent Transcriptional Bypass of DNA Alkyl Phosphotriester Adducts in Mammalian Cells","volume":"2","author":"Tan","year":"2022","journal-title":"DNA"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.molcel.2012.04.009","article-title":"R loops: From transcription byproducts to threats to genome stability","volume":"46","author":"Aguilera","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.molcel.2018.06.037","article-title":"Genome-wide Map of R-Loop-induced damage reveals how a subset of R-loops contributes to genomic instability","volume":"71","author":"Costantino","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"4612","DOI":"10.1093\/nar\/gkz165","article-title":"RNase H activities counteract a toxic effect of Polymerase \u03b7 in cells replicating with depleted dNTP pools","volume":"47","author":"Meroni","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1046\/j.0818-9641.2004.01221.x","article-title":"Human DNA polymerase-\u03b7, an A-T mutator in somatic hypermutation of rearranged immunoglobulin genes, is a reverse transcriptase","volume":"82","author":"Franklin","year":"2004","journal-title":"Immunol. Cell Biol."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/cr.2008.1","article-title":"Homologous recombination in DNA repair and DNA damage tolerance","volume":"18","author":"Li","year":"2008","journal-title":"Cell Res."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1126\/science.7605428","article-title":"Specific association of human telomerase activity with immortal cells and cancer","volume":"266","author":"Kim","year":"1994","journal-title":"Science"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1038\/nm1197-1271","article-title":"Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines","volume":"3","author":"Bryan","year":"1997","journal-title":"Nat. Med."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"108436","DOI":"10.1016\/j.mrrev.2022.108436","article-title":"Current state of knowledge of human DNA polymerase \u03b7 protein structure and disease-causing mutations","volume":"790","author":"Feltes","year":"2022","journal-title":"Mut. Res.-Rev."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.mrfmmm.2013.03.001","article-title":"Biochemical analysis of active site mutations of human polymerase \u03b7","volume":"745\u2013746","author":"Suarez","year":"2013","journal-title":"Mut. Res."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1002\/em.21857","article-title":"Detrimental effects of UV-B radiation in a xeroderma pigmentosum-variant cell line","volume":"55","author":"Herman","year":"2014","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1002\/em.21807","article-title":"Mutation of the Little Finger Domain in Human DNA Polymerase eta Alters Fidelity When Copying Undamaged DNA","volume":"54","author":"Beardslee","year":"2013","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.dnarep.2015.02.017","article-title":"Aberrant C-terminal domain of polymerase \u03b7 targets the functional enzyme to the proteosomal degradation pathway","volume":"29","author":"Pouvelle","year":"2015","journal-title":"DNA Repair"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/humu.22462","article-title":"Correlation of phenotype\/genotype in a cohort of 23 xeroderma pigmentosum-variant patients reveals 12 new disease-causing POLH mutations","volume":"35","author":"Opletalova","year":"2014","journal-title":"Human Mut."},{"key":"ref_190","first-page":"173","article-title":"Diagnosis of xeroderma pigmentosum variant in a young patient with two novel mutations in the POLH gene","volume":"2511","author":"Morren","year":"2017","journal-title":"Am. J. Med. Genet."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"3228","DOI":"10.1016\/j.ejca.2009.04.034","article-title":"Variants of the xeroderma pigmentosum variant gene (POLH) are associated with melanoma risk","volume":"45","author":"Guedj","year":"2009","journal-title":"Eur. J. Cancer"},{"key":"ref_192","doi-asserted-by":"crossref","unstructured":"Makridakis, N.M., and Reichardt, J.K.V. (2012). Translesion DNA polymerases and cancer. Front. Genet., 3.","DOI":"10.3389\/fgene.2012.00174"},{"key":"ref_193","doi-asserted-by":"crossref","unstructured":"Yeom, M., Hong, J.-K., Shin, J.-H., Lee, Y., Guengerich, F.P., and Choi, J.-Y. (2023). Identification of three human POLH germline variants defective in complementing the UV- and cisplatin-sensitivity of POLH-deficient cells. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065198"},{"key":"ref_194","doi-asserted-by":"crossref","unstructured":"Zhou, W., Chen, Y.W., Liu, X., Chu, P., Loria, S., Wang, Y., Yen, Y., and Chou, K.M. (2013). Expression of DNA translesion synthesis polymerase eta in head and neck squamous cell cancer predicts resistance to gemcitabine and cisplatin-based chemotherapy. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0083978"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1080\/13543784.2021.1850692","article-title":"Translesion synthesis inhibitors as a new class of cancer chemotherapeutics","volume":"30","author":"Patel","year":"2021","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_196","first-page":"20","article-title":"Targeting DNA repair in cancer: Beyond PARP inhibitors","volume":"10","author":"Cantor","year":"2020","journal-title":"Cancer Discov."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/10\/1271\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:05:25Z","timestamp":1760112325000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/10\/1271"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,27]]},"references-count":196,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["genes15101271"],"URL":"https:\/\/doi.org\/10.3390\/genes15101271","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,27]]}}}