Skip to main content
SpringerLink
Log in

Translesion DNA Synthesis

  • Chapter
  • First Online:
DNA Repair Disorders

  • 707 Accesses

Abstract

Human DNA polymerase η (pol η) is the gene product that is altered in the variant form of xeroderma pigmentosum. Pol η has a structure that can accommodate the cyclobutane pyrimidine dimer, the most prominent ultraviolet-induced DNA lesion. Pol η catalyzes efficient and accurate translesion DNA synthesis (TLS) under the fine control of systems involving interactions with mono-ubiquitinated proliferating cell nuclear antigen. Pol η can also catalyze TLS past cisplatin lesions, which might contribute to the resistance of tumors to chemotherapy. Other Y-family polymerases, pol ι, pol κ, and REV1, and a B-family polymerase pol ζ can contribute to erroneous TLS past ultraviolet-induced lesions. However, these polymerases also contribute to the maintenance of genomic stability in the presence of their cognate DNA lesions. A-family polymerases, pol θ and pol ν, also have TLS abilities, and pol θ has an important role in an alternative end-joining repair pathway for DNA double-strand breaks, protecting against genomic instability. PrimPol is a protein with DNA polymerase and primase activities that is capable of initiating de novo DNA/RNA synthesis and that also has the capacity to bypass modifications that stall the replisome, by TLS or origin-independent re-priming. This chapter summarizes our current knowledge relating to DNA polymerases that are capable of catalyzing TLS.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ohmori H, Friedberg EC, Fuchs RP, Goodman MF, Hanaoka F, Hinkle D, Kunkel TA, Lawrence CW, Livneh Z, Nohmi T, et al. The Y-family of DNA polymerases. Mol Cell. 2001;8:7–8.

    Article  CAS  PubMed  Google Scholar 

  2. Johnson RE, Prakash S, Prakash L. Efficient bypass of a thymine-thymine dimer by yeast DNA polymerase poleta. Science. 1999;283:1001–4.

    Article  CAS  PubMed  Google Scholar 

  3. Masutani C, Araki M, Yamada A, Kusumoto R, Nogimori T, Maekawa T, Iwai S, Hanaoka F. Xeroderma pigmentosum variant (XP-V) correcting protein from HeLa cells has a thymine dimer bypass DNA polymerase activity. EMBO J. 1999;18:3491–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Masutani C, Kusumoto R, Yamada A, Dohmae N, Yokoi M, Yuasa M, Araki M, Iwai S, Takio K, Hanaoka F. The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta. Nature. 1999;399:700–4.

    Article  CAS  PubMed  Google Scholar 

  5. Johnson RE, Kondratick CM, Prakash S, Prakash L. hRAD30 mutations in the variant form of xeroderma pigmentosum. Science. 1999;285:263–5.

    Article  CAS  PubMed  Google Scholar 

  6. Kannouche P, Broughton BC, Volker M, Hanaoka F, Mullenders LH, Lehmann AR. Domain structure, localization, and function of DNA polymerase eta, defective in xeroderma pigmentosum variant cells. Genes Dev. 2001;15:158–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Yamada A, Masutani C, Iwai S, Hanaoka F. Complementation of defective translesion synthesis and UV light sensitivity in xeroderma pigmentosum variant cells by human and mouse DNA polymerase eta. Nucleic Acids Res. 2000;28:2473–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Johnson RE, Washington MT, Prakash S, Prakash L. Fidelity of human DNA polymerase eta. J Biol Chem. 2000;275:7447–50.

    Article  CAS  PubMed  Google Scholar 

  9. Masutani C, Kusumoto R, Iwai S, Hanaoka F. Mechanisms of accurate translesion synthesis by human DNA polymerase eta. EMBO J. 2000;19:3100–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kusumoto R, Masutani C, Shimmyo S, Iwai S, Hanaoka F. DNA binding properties of human DNA polymerase eta: implications for fidelity and polymerase switching of translesion synthesis. Genes Cells. 2004;9:1139–50.

    Article  CAS  PubMed  Google Scholar 

  11. McCulloch SD, Kokoska RJ, Masutani C, Iwai S, Hanaoka F, Kunkel TA. Preferential cis-syn thymine dimer bypass by DNA polymerase eta occurs with biased fidelity. Nature. 2004;428:97–100.

    Article  CAS  PubMed  Google Scholar 

  12. Biertumpfel C, Zhao Y, Kondo Y, Ramon-Maiques S, Gregory M, Lee JY, Masutani C, Lehmann AR, Hanaoka F, Yang W. Structure and mechanism of human DNA polymerase eta. Nature. 2010;465:1044–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Nakamura T, Zhao Y, Yamagata Y, Hua YJ, Yang W. Watching DNA polymerase eta make a phosphodiester bond. Nature. 2012;487:196–201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ucisik MN, Hammes-Schiffer S. Relative binding free energies of adenine and guanine to damaged and undamaged DNA in human DNA polymerase eta: clues for fidelity and overall efficiency. J Am Chem Soc. 2015;137:13240–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Johnson RE, Haracska L, Prakash S, Prakash L. Role of DNA polymerase eta in the bypass of a (6-4) TT photoproduct. Mol Cell Biol. 2001;21:3558–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Yoon JH, Prakash L, Prakash S. Error-free replicative bypass of (6-4) photoproducts by DNA polymerase zeta in mouse and human cells. Genes Dev. 2010;24:123–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Naegeli H, Sugasawa K. The xeroderma pigmentosum pathway: decision tree analysis of DNA quality. DNA Repair (Amst). 2011;10:673–83.

    Article  CAS  Google Scholar 

  18. Lin Q, Clark AB, McCulloch SD, Yuan T, Bronson RT, Kunkel TA, Kucherlapati R. Increased susceptibility to UV-induced skin carcinogenesis in polymerase eta-deficient mice. Cancer Res. 2006;66:87–94.

    Article  CAS  PubMed  Google Scholar 

  19. Ohkumo T, Kondo Y, Yokoi M, Tsukamoto T, Yamada A, Sugimoto T, Kanao R, Higashi Y, Kondoh H, Tatematsu M, et al. UV-B radiation induces epithelial tumors in mice lacking DNA polymerase eta and mesenchymal tumors in mice deficient for DNA polymerase iota. Mol Cell Biol. 2006;26:7696–706.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ikehata H, Chang Y, Yokoi M, Yamamoto M, Hanaoka F. Remarkable induction of UV-signature mutations at the 3′-cytosine of dipyrimidine sites except at 5′-TCG-3′ in the UVB-exposed skin epidermis of xeroderma pigmentosum variant model mice. DNA Repair (Amst). 2014;22:112–22.

    Article  CAS  Google Scholar 

  21. Kanao R, Yokoi M, Ohkumo T, Sakurai Y, Dotsu K, Kura S, Nakatsu Y, Tsuzuki T, Masutani C, Hanaoka F. UV-induced mutations in epidermal cells of mice defective in DNA polymerase eta and/or iota. DNA Repair (Amst). 2015;29:139–46.

    Article  CAS  Google Scholar 

  22. Ito W, Yokoi M, Sakayoshi N, Sakurai Y, Akagi J, Mitani H, Hanaoka F. Stalled Poleta at its cognate substrate initiates an alternative translesion synthesis pathway via interaction with REV1. Genes Cells. 2012;17:98–108.

    Article  CAS  PubMed  Google Scholar 

  23. Matsuda T, Bebenek K, Masutani C, Hanaoka F, Kunkel TA. Low fidelity DNA synthesis by human DNA polymerase-eta. Nature. 2000;404:1011–3.

    Article  CAS  PubMed  Google Scholar 

  24. Matsuda T, Bebenek K, Masutani C, Rogozin IB, Hanaoka F, Kunkel TA. Error rate and specificity of human and murine DNA polymerase eta. J Mol Biol. 2001;312:335–46.

    Article  CAS  PubMed  Google Scholar 

  25. King NM, Nikolaishvili-Feinberg N, Bryant MF, Luche DD, Heffernan TP, Simpson DA, Hanaoka F, Kaufmann WK, Cordeiro-Stone M. Overproduction of DNA polymerase eta does not raise the spontaneous mutation rate in diploid human fibroblasts. DNA Repair (Amst). 2005;4:714–24.

    Article  CAS  Google Scholar 

  26. Bebenek K, Matsuda T, Masutani C, Hanaoka F, Kunkel TA. Proofreading of DNA polymerase eta-dependent replication errors. J Biol Chem. 2001;276:2317–20.

    Article  CAS  PubMed  Google Scholar 

  27. Avkin S, Livneh Z. Efficiency, specificity and DNA polymerase-dependence of translesion replication across the oxidative DNA lesion 8-oxoguanine in human cells. Mutat Res. 2002;510:81–90.

    Article  CAS  PubMed  Google Scholar 

  28. Haracska L, Yu SL, Johnson RE, Prakash L, Prakash S. Efficient and accurate replication in the presence of 7,8-dihydro-8-oxoguanine by DNA polymerase eta. Nat Genet. 2000;25:458–61.

    Article  CAS  PubMed  Google Scholar 

  29. Su Y, Patra A, Harp JM, Egli M, Guengerich FP. Roles of residues Arg-61 and Gln-38 of human DNA polymerase eta in bypass of deoxyguanosine and 7,8-Dihydro-8-oxo-2′-deoxyguanosine. J Biol Chem. 2015;290:15921–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zhang Y, Yuan F, Wu X, Rechkoblit O, Taylor JS, Geacintov NE, Wang Z. Error-prone lesion bypass by human DNA polymerase eta. Nucleic Acids Res. 2000;28:4717–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Patra A, Zhang Q, Guengerich FP, Egli M. Mechanisms of insertion of dCTP and dTTP opposite the DNA lesion O6-methyl-2′-deoxyguanosine by human DNA polymerase eta. J Biol Chem. 2016;291(46):24304–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Chiapperino D, Kroth H, Kramarczuk IH, Sayer JM, Masutani C, Hanaoka F, Jerina DM, Cheh AM. Preferential misincorporation of purine nucleotides by human DNA polymerase eta opposite benzo[a]pyrene 7,8-diol 9,10-epoxide deoxyguanosine adducts. J Biol Chem. 2002;277:11765–71.

    Article  CAS  PubMed  Google Scholar 

  33. Haracska L, Washington MT, Prakash S, Prakash L. Inefficient bypass of an abasic site by DNA polymerase eta. J Biol Chem. 2001;276:6861–6.

    Article  CAS  PubMed  Google Scholar 

  34. Kusumoto R, Masutani C, Iwai S, Hanaoka F. Translesion synthesis by human DNA polymerase eta across thymine glycol lesions. Biochemistry. 2002;41:6090–9.

    Article  CAS  PubMed  Google Scholar 

  35. Patra A, Zhang Q, Lei L, Su Y, Egli M, Guengerich FP. Structural and kinetic analysis of nucleoside triphosphate incorporation opposite an abasic site by human translesion DNA polymerase eta. J Biol Chem. 2015;290:8028–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Yasui M, Dong H, Bonala RR, Suzuki N, Ohmori H, Hanaoka F, Johnson F, Grollman AP, Shibutani S. Mutagenic properties of 3-(deoxyguanosin-N2-yl)-2-acetylaminofluorene, a persistent acetylaminofluorene-derived DNA adduct in mammalian cells. Biochemistry. 2004;43:15005–13.

    Article  CAS  PubMed  Google Scholar 

  37. Zhang Y, Wu X, Guo D, Rechkoblit O, Geacintov NE, Wang Z. Two-step error-prone bypass of the (+)- and (−)-trans-anti-BPDE-N2-dG adducts by human DNA polymerases eta and kappa. Mutat Res. 2002;510:23–35.

    Article  CAS  PubMed  Google Scholar 

  38. Vaisman A, Masutani C, Hanaoka F, Chaney SG. Efficient translesion replication past oxaliplatin and cisplatin GpG adducts by human DNA polymerase eta. Biochemistry. 2000;39:4575–80.

    Article  CAS  PubMed  Google Scholar 

  39. Zhao Y, Biertumpfel C, Gregory MT, Hua YJ, Hanaoka F, Yang W. Structural basis of human DNA polymerase eta-mediated chemoresistance to cisplatin. Proc Natl Acad Sci U S A. 2012;109:7269–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Alt A, Lammens K, Chiocchini C, Lammens A, Pieck JC, Kuch D, Hopfner KP, Carell T. Bypass of DNA lesions generated during anticancer treatment with cisplatin by DNA polymerase eta. Science. 2007;318:967–70.

    Article  CAS  PubMed  Google Scholar 

  41. Lee YS, Gregory MT, Yang W. Human Pol zeta purified with accessory subunits is active in translesion DNA synthesis and complements Pol eta in cisplatin bypass. Proc Natl Acad Sci U S A. 2014;111:2954–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Shachar S, Ziv O, Avkin S, Adar S, Wittschieben J, Reissner T, Chaney S, Friedberg EC, Wang Z, Carell T, et al. Two-polymerase mechanisms dictate error-free and error-prone translesion DNA synthesis in mammals. EMBO J. 2009;28:383–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Albertella MR, Green CM, Lehmann AR, O’Connor MJ. A role for polymerase eta in the cellular tolerance to cisplatin-induced damage. Cancer Res. 2005;65:9799–806.

    Article  CAS  PubMed  Google Scholar 

  44. Bassett E, King NM, Bryant MF, Hector S, Pendyala L, Chaney SG, Cordeiro-Stone M. The role of DNA polymerase eta in translesion synthesis past platinum-DNA adducts in human fibroblasts. Cancer Res. 2004;64:6469–75.

    Article  CAS  PubMed  Google Scholar 

  45. Prakash S, Johnson RE, Prakash L. Eukaryotic translesion synthesis DNA polymerases: specificity of structure and function. Annu Rev Biochem. 2005;74:317–53.

    Article  CAS  PubMed  Google Scholar 

  46. Sale JE, Lehmann AR, Woodgate R. Y-family DNA polymerases and their role in tolerance of cellular DNA damage. Nat Rev Mol Cell Biol. 2012;13:141–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Yang W. Damage repair DNA polymerases Y. Curr Opin Struct Biol. 2003;13:23–30.

    Article  CAS  PubMed  Google Scholar 

  48. Acharya N, Yoon JH, Hurwitz J, Prakash L, Prakash S. DNA polymerase eta lacking the ubiquitin-binding domain promotes replicative lesion bypass in humans cells. Proc Natl Acad Sci U S A. 2010;107:10401–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Bienko M, Green CM, Crosetto N, Rudolf F, Zapart G, Coull B, Kannouche P, Wider G, Peter M, Lehmann AR, et al. Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis. Science. 2005;310:1821–4.

    Article  CAS  PubMed  Google Scholar 

  50. Kannouche PL, Wing J, Lehmann AR. Interaction of human DNA polymerase eta with monoubiquitinated PCNA: a possible mechanism for the polymerase switch in response to DNA damage. Mol Cell. 2004;14:491–500.

    Article  CAS  PubMed  Google Scholar 

  51. Masuda Y, Kanao R, Kaji K, Ohmori H, Hanaoka F, Masutani C. Different types of interaction between PCNA and PIP boxes contribute to distinct cellular functions of Y-family DNA polymerases. Nucleic Acids Res. 2015;43:7898–910.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Acharya N, Yoon JH, Gali H, Unk I, Haracska L, Johnson RE, Hurwitz J, Prakash L, Prakash S. Roles of PCNA-binding and ubiquitin-binding domains in human DNA polymerase eta in translesion DNA synthesis. Proc Natl Acad Sci U S A. 2008;105:17724–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Broughton BC, Cordonnier A, Kleijer WJ, Jaspers NG, Fawcett H, Raams A, Garritsen VH, Stary A, Avril MF, Boudsocq F, et al. Molecular analysis of mutations in DNA polymerase eta in xeroderma pigmentosum-variant patients. Proc Natl Acad Sci U S A. 2002;99:815–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Inui H, Oh KS, Nadem C, Ueda T, Khan SG, Metin A, Gozukara E, Emmert S, Slor H, Busch DB, et al. Xeroderma pigmentosum-variant patients from America, Europe, and Asia. J Invest Dermatol. 2008;128:2055–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Ono R, Masaki T, Takeuchi S, Shimizu A, Tanioka M, Kambe N, Matsue H, Kamide R, Nishigori C. Three school-age cases of xeroderma pigmentosum variant type. Photodermatol Photoimmunol Photomed. 2013;29:132–9.

    Article  CAS  PubMed  Google Scholar 

  56. Opletalova K, Bourillon A, Yang W, Pouvelle C, Armier J, Despras E, Ludovic M, Mateus C, Robert C, Kannouche P, et al. Correlation of phenotype/genotype in a cohort of 23 xeroderma pigmentosum-variant patients reveals 12 new disease-causing POLH mutations. Hum Mutat. 2014;35:117–28.

    Article  CAS  PubMed  Google Scholar 

  57. Tanioka M, Masaki T, Ono R, Nagano T, Otoshi-Honda E, Matsumura Y, Takigawa M, Inui H, Miyachi Y, Moriwaki S, et al. Molecular analysis of DNA polymerase eta gene in Japanese patients diagnosed as xeroderma pigmentosum variant type. J Invest Dermatol. 2007;127:1745–51.

    Article  CAS  PubMed  Google Scholar 

  58. Ahmed-Seghir S, Pouvelle C, Despras E, Cordonnier A, Sarasin A, Kannouche PL. Aberrant C-terminal domain of polymerase eta targets the functional enzyme to the proteosomal degradation pathway. DNA Repair (Amst). 2015;29:154–65.

    Article  CAS  Google Scholar 

  59. McDonald JP, Rapic-Otrin V, Epstein JA, Broughton BC, Wang X, Lehmann AR, Wolgemuth DJ, Woodgate R. Novel human and mouse homologs of Saccharomyces cerevisiae DNA polymerase eta. Genomics. 1999;60:20–30.

    Article  CAS  PubMed  Google Scholar 

  60. Tissier A, McDonald JP, Frank EG, Woodgate R. Poliota, a remarkably error-prone human DNA polymerase. Genes Dev. 2000;14:1642–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Zhang Y, Yuan F, Wu X, Wang Z. Preferential incorporation of G opposite template T by the low-fidelity human DNA polymerase iota. Mol Cell Biol. 2000;20:7099–108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Johnson RE, Prakash L, Prakash S. Biochemical evidence for the requirement of Hoogsteen base pairing for replication by human DNA polymerase iota. Proc Natl Acad Sci U S A. 2005;102:10466–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Nair DT, Johnson RE, Prakash L, Prakash S, Aggarwal AK. An incoming nucleotide imposes an anti to syn conformational change on the templating purine in the human DNA polymerase-iota active site. Structure. 2006;14:749–55.

    Article  CAS  PubMed  Google Scholar 

  64. Nair DT, Johnson RE, Prakash S, Prakash L, Aggarwal AK. Replication by human DNA polymerase-iota occurs by Hoogsteen base-pairing. Nature. 2004;430:377–80.

    Article  CAS  PubMed  Google Scholar 

  65. Choi JY, Lim S, Eoff RL, Guengerich FP. Kinetic analysis of base-pairing preference for nucleotide incorporation opposite template pyrimidines by human DNA polymerase iota. J Mol Biol. 2009;389:264–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Kirouac KN, Ling H. Structural basis of error-prone replication and stalling at a thymine base by human DNA polymerase iota. EMBO J. 2009;28:1644–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Vaisman A, Takasawa K, Iwai S, Woodgate R. DNA polymerase iota-dependent translesion replication of uracil containing cyclobutane pyrimidine dimers. DNA Repair (Amst). 2006;5:210–8.

    Article  CAS  Google Scholar 

  68. Vaisman A, Woodgate R. Unique misinsertion specificity of poliota may decrease the mutagenic potential of deaminated cytosines. EMBO J. 2001;20:6520–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Tissier A, Frank EG, McDonald JP, Iwai S, Hanaoka F, Woodgate R. Misinsertion and bypass of thymine-thymine dimers by human DNA polymerase iota. EMBO J. 2000;19:5259–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Zhang Y, Yuan F, Wu X, Taylor JS, Wang Z. Response of human DNA polymerase iota to DNA lesions. Nucleic Acids Res. 2001;29:928–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Choi JY, Guengerich FP. Kinetic evidence for inefficient and error-prone bypass across bulky N2-guanine DNA adducts by human DNA polymerase iota. J Biol Chem. 2006;281:12315–24.

    Article  CAS  PubMed  Google Scholar 

  72. Pence MG, Blans P, Zink CN, Hollis T, Fishbein JC, Perrino FW. Lesion bypass of N2-ethylguanine by human DNA polymerase iota. J Biol Chem. 2009;284:1732–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Washington MT, Minko IG, Johnson RE, Haracska L, Harris TM, Lloyd RS, Prakash S, Prakash L. Efficient and error-free replication past a minor-groove N2-guanine adduct by the sequential action of yeast Rev1 and DNA polymerase zeta. Mol Cell Biol. 2004;24:6900–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Kirouac KN, Ling H. Unique active site promotes error-free replication opposite an 8-oxo-guanine lesion by human DNA polymerase iota. Proc Natl Acad Sci U S A. 2011;108:3210–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Hampp S, Kiessling T, Buechle K, Mansilla SF, Thomale J, Rall M, Ahn J, Pospiech H, Gottifredi V, Wiesmuller L. DNA damage tolerance pathway involving DNA polymerase iota and the tumor suppressor p53 regulates DNA replication fork progression. Proc Natl Acad Sci U S A. 2016;113:E4311–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. McDonald JP, Frank EG, Plosky BS, Rogozin IB, Masutani C, Hanaoka F, Woodgate R, Gearhart PJ. 129-derived strains of mice are deficient in DNA polymerase iota and have normal immunoglobulin hypermutation. J Exp Med. 2003;198:635–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Aoufouchi S, De Smet A, Delbos F, Gelot C, Guerrera IC, Weill JC, Reynaud CA. 129-derived mouse strains express an unstable but catalytically active DNA polymerase iota variant. Mol Cell Biol. 2015;35:3059–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Dumstorf CA, Clark AB, Lin Q, Kissling GE, Yuan T, Kucherlapati R, McGregor WG, Kunkel TA. Participation of mouse DNA polymerase iota in strand-biased mutagenic bypass of UV photoproducts and suppression of skin cancer. Proc Natl Acad Sci U S A. 2006;103:18083–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Gueranger Q, Stary A, Aoufouchi S, Faili A, Sarasin A, Reynaud CA, Weill JC. Role of DNA polymerases eta, iota and zeta in UV resistance and UV-induced mutagenesis in a human cell line. DNA Repair (Amst). 2008;7:1551–62.

    Article  CAS  Google Scholar 

  80. Wang Y, Woodgate R, McManus TP, Mead S, McCormick JJ, Maher VM. Evidence that in xeroderma pigmentosum variant cells, which lack DNA polymerase eta, DNA polymerase iota causes the very high frequency and unique spectrum of UV-induced mutations. Cancer Res. 2007;67:3018–26.

    Article  CAS  PubMed  Google Scholar 

  81. Ziv O, Geacintov N, Nakajima S, Yasui A, Livneh Z. DNA polymerase zeta cooperates with polymerases kappa and iota in translesion DNA synthesis across pyrimidine photodimers in cells from XPV patients. Proc Natl Acad Sci U S A. 2009;106:11552–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Maul RW, MacCarthy T, Frank EG, Donigan KA, McLenigan MP, Yang W, Saribasak H, Huston DE, Lange SS, Woodgate R, et al. DNA polymerase iota functions in the generation of tandem mutations during somatic hypermutation of antibody genes. J Exp Med. 2016;213:1675–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Martomo SA, Yang WW, Vaisman A, Maas A, Yokoi M, Hoeijmakers JH, Hanaoka F, Woodgate R, Gearhart PJ. Normal hypermutation in antibody genes from congenic mice defective for DNA polymerase iota. DNA Repair (Amst). 2006;5:392–8.

    Article  CAS  Google Scholar 

  84. Gerlach VL, Aravind L, Gotway G, Schultz RA, Koonin EV, Friedberg EC. Human and mouse homologs of Escherichia coli DinB (DNA polymerase IV), members of the UmuC/DinB superfamily. Proc Natl Acad Sci U S A. 1999;96:11922–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Johnson RE, Prakash S, Prakash L. The human DINB1 gene encodes the DNA polymerase Poltheta. Proc Natl Acad Sci U S A. 2000;97:3838–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Ogi T, Kato T Jr, Kato T, Ohmori H. Mutation enhancement by DINB1, a mammalian homologue of the Escherichia coli mutagenesis protein dinB. Genes Cells. 1999;4:607–18.

    Article  CAS  PubMed  Google Scholar 

  87. Ohashi E, Ogi T, Kusumoto R, Iwai S, Masutani C, Hanaoka F, Ohmori H. Error-prone bypass of certain DNA lesions by the human DNA polymerase kappa. Genes Dev. 2000;14:1589–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Zhang Y, Yuan F, Xin H, Wu X, Rajpal DK, Yang D, Wang Z. Human DNA polymerase kappa synthesizes DNA with extraordinarily low fidelity. Nucleic Acids Res. 2000;28:4147–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Bavoux C, Leopoldino AM, Bergoglio V, O-Wang J, Ogi T, Bieth A, Judde JG, Pena SD, Poupon MF, Helleday T, et al. Up-regulation of the error-prone DNA polymerase kappa promotes pleiotropic genetic alterations and tumorigenesis. Cancer Res. 2005;65:325–30.

    CAS  PubMed  Google Scholar 

  90. Ogi T, Mimura J, Hikida M, Fujimoto H, Fujii-Kuriyama Y, Ohmori H. Expression of human and mouse genes encoding polkappa: testis-specific developmental regulation and AhR-dependent inducible transcription. Genes Cells. 2001;6:943–53.

    Article  CAS  PubMed  Google Scholar 

  91. Velasco-Miguel S, Richardson JA, Gerlach VL, Lai WC, Gao T, Russell LD, Hladik CL, White CL, Friedberg EC. Constitutive and regulated expression of the mouse Dinb (Polkappa) gene encoding DNA polymerase kappa. DNA Repair (Amst). 2003;2:91–106.

    Article  CAS  Google Scholar 

  92. Gerlach VL, Feaver WJ, Fischhaber PL, Friedberg EC. Purification and characterization of pol kappa, a DNA polymerase encoded by the human DINB1 gene. J Biol Chem. 2001;276:92–8.

    Article  CAS  PubMed  Google Scholar 

  93. Washington MT, Johnson RE, Prakash L, Prakash S. Human DINB1-encoded DNA polymerase kappa is a promiscuous extender of mispaired primer termini. Proc Natl Acad Sci U S A. 2002;99:1910–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Zhang Y, Yuan F, Wu X, Wang M, Rechkoblit O, Taylor JS, Geacintov NE, Wang Z. Error-free and error-prone lesion bypass by human DNA polymerase kappa in vitro. Nucleic Acids Res. 2000;28:4138–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Suzuki N, Ohashi E, Hayashi K, Ohmori H, Grollman AP, Shibutani S. Translesional synthesis past acetylaminofluorene-derived DNA adducts catalyzed by human DNA polymerase kappa and Escherichia coli DNA polymerase IV. Biochemistry. 2001;40:15176–83.

    Article  CAS  PubMed  Google Scholar 

  96. Fischhaber PL, Gerlach VL, Feaver WJ, Hatahet Z, Wallace SS, Friedberg EC. Human DNA polymerase kappa bypasses and extends beyond thymine glycols during translesion synthesis in vitro, preferentially incorporating correct nucleotides. J Biol Chem. 2002;277:37604–11.

    Article  CAS  PubMed  Google Scholar 

  97. Rechkoblit O, Zhang Y, Guo D, Wang Z, Amin S, Krzeminsky J, Louneva N, Geacintov NE. Trans-lesion synthesis past bulky benzo[a]pyrene diol epoxide N2-dG and N6-dA lesions catalyzed by DNA bypass polymerases. J Biol Chem. 2002;277:30488–94.

    Article  CAS  PubMed  Google Scholar 

  98. Suzuki N, Itoh S, Poon K, Masutani C, Hanaoka F, Ohmori H, Yoshizawa I, Shibutani S. Translesion synthesis past estrogen-derived DNA adducts by human DNA polymerases eta and kappa. Biochemistry. 2004;43:6304–11.

    Article  CAS  PubMed  Google Scholar 

  99. Suzuki N, Ohashi E, Kolbanovskiy A, Geacintov NE, Grollman AP, Ohmori H, Shibutani S. Translesion synthesis by human DNA polymerase kappa on a DNA template containing a single stereoisomer of dG-(+)- or dG-(−)-anti-N(2)-BPDE (7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene). Biochemistry. 2002;41:6100–6.

    Article  CAS  PubMed  Google Scholar 

  100. Jha V, Bian C, Xing G, Ling H. Structure and mechanism of error-free replication past the major benzo[a]pyrene adduct by human DNA polymerase kappa. Nucleic Acids Res. 2016;44:4957–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Ohashi E, Bebenek K, Matsuda T, Feaver WJ, Gerlach VL, Friedberg EC, Ohmori H, Kunkel TA. Fidelity and processivity of DNA synthesis by DNA polymerase kappa, the product of the human DINB1 gene. J Biol Chem. 2000;275:39678–84.

    Article  CAS  PubMed  Google Scholar 

  102. Wolfle WT, Washington MT, Prakash L, Prakash S. Human DNA polymerase kappa uses template-primer misalignment as a novel means for extending mispaired termini and for generating single-base deletions. Genes Dev. 2003;17:2191–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Haracska L, Prakash L, Prakash S. Role of human DNA polymerase kappa as an extender in translesion synthesis. Proc Natl Acad Sci U S A. 2002;99:16000–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Schenten D, Gerlach VL, Guo C, Velasco-Miguel S, Hladik CL, White CL, Friedberg EC, Rajewsky K, Esposito G. DNA polymerase kappa deficiency does not affect somatic hypermutation in mice. Eur J Immunol. 2002;32:3152–60.

    Article  CAS  PubMed  Google Scholar 

  105. Bi X, Slater DM, Ohmori H, Vaziri C. DNA polymerase kappa is specifically required for recovery from the benzo[a]pyrene-dihydrodiol epoxide (BPDE)-induced S-phase checkpoint. J Biol Chem. 2005;280:22343–55.

    Article  CAS  PubMed  Google Scholar 

  106. Ogi T, Shinkai Y, Tanaka K, Ohmori H. Polkappa protects mammalian cells against the lethal and mutagenic effects of benzo[a]pyrene. Proc Natl Acad Sci U S A. 2002;99:15548–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Stancel JN, McDaniel LD, Velasco S, Richardson J, Guo C, Friedberg EC. Polk mutant mice have a spontaneous mutator phenotype. DNA Repair (Amst). 2009;8:1355–62.

    Article  CAS  Google Scholar 

  108. Avkin S, Goldsmith M, Velasco-Miguel S, Geacintov N, Friedberg EC, Livneh Z. Quantitative analysis of translesion DNA synthesis across a benzo[a]pyrene-guanine adduct in mammalian cells: the role of DNA polymerase kappa. J Biol Chem. 2004;279:53298–305.

    Article  CAS  PubMed  Google Scholar 

  109. Yoon JH, Prakash L, Prakash S. Highly error-free role of DNA polymerase eta in the replicative bypass of UV-induced pyrimidine dimers in mouse and human cells. Proc Natl Acad Sci U S A. 2009;106:18219–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Yoon JH, Prakash S, Prakash L. Genetic control of translesion synthesis on leading and lagging DNA strands in plasmids derived from Epstein-Barr virus in human cells. MBio. 2012;3:e00271–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Gibbs PE, Wang XD, Li Z, McManus TP, McGregor WG, Lawrence CW, Maher VM. The function of the human homolog of Saccharomyces cerevisiae REV1 is required for mutagenesis induced by UV light. Proc Natl Acad Sci U S A. 2000;97:4186–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Lin W, Xin H, Zhang Y, Wu X, Yuan F, Wang Z. The human REV1 gene codes for a DNA template-dependent dCMP transferase. Nucleic Acids Res. 1999;27:4468–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Masuda Y, Takahashi M, Fukuda S, Sumii M, Kamiya K. Mechanisms of dCMP transferase reactions catalyzed by mouse Rev1 protein. J Biol Chem. 2002;277:3040–6.

    Article  CAS  PubMed  Google Scholar 

  114. Masuda Y, Kamiya K. Biochemical properties of the human REV1 protein. FEBS Lett. 2002;520:88–92.

    Article  CAS  PubMed  Google Scholar 

  115. Zhang Y, Wu X, Rechkoblit O, Geacintov NE, Taylor JS, Wang Z. Response of human REV1 to different DNA damage: preferential dCMP insertion opposite the lesion. Nucleic Acids Res. 2002;30:1630–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Lin X, Okuda T, Trang J, Howell SB. Human REV1 modulates the cytotoxicity and mutagenicity of cisplatin in human ovarian carcinoma cells. Mol Pharmacol. 2006;69:1748–54.

    Article  CAS  PubMed  Google Scholar 

  117. Sharma S, Hicks JK, Chute CL, Brennan JR, Ahn JY, Glover TW, Canman CE. REV1 and polymerase zeta facilitate homologous recombination repair. Nucleic Acids Res. 2012;40:682–91.

    Article  CAS  PubMed  Google Scholar 

  118. Jansen JG, Langerak P, Tsaalbi-Shtylik A, van den Berk P, Jacobs H, de Wind N. Strand-biased defect in C/G transversions in hypermutating immunoglobulin genes in Rev1-deficient mice. J Exp Med. 2006;203:319–23.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Jansen JG, Tsaalbi-Shtylik A, Langerak P, Calleja F, Meijers CM, Jacobs H, de Wind N. The BRCT domain of mammalian Rev1 is involved in regulating DNA translesion synthesis. Nucleic Acids Res. 2005;33:356–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Masuda K, Ouchida R, Li Y, Gao X, Mori H, Wang JY. A critical role for REV1 in regulating the induction of C:G transitions and A:T mutations during Ig gene hypermutation. J Immunol. 2009;183:1846–50.

    Article  CAS  PubMed  Google Scholar 

  121. Tsaalbi-Shtylik A, Verspuy JW, Jansen JG, Rebel H, Carlee LM, van der Valk MA, Jonkers J, de Gruijl FR, de Wind N. Error-prone translesion replication of damaged DNA suppresses skin carcinogenesis by controlling inflammatory hyperplasia. Proc Natl Acad Sci U S A. 2009;106:21836–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Guo C, Fischhaber PL, Luk-Paszyc MJ, Masuda Y, Zhou J, Kamiya K, Kisker C, Friedberg EC. Mouse Rev1 protein interacts with multiple DNA polymerases involved in translesion DNA synthesis. EMBO J. 2003;22:6621–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Hara K, Hashimoto H, Murakumo Y, Kobayashi S, Kogame T, Unzai S, Akashi S, Takeda S, Shimizu T, Sato M. Crystal structure of human REV7 in complex with a human REV3 fragment and structural implication of the interaction between DNA polymerase zeta and REV1. J Biol Chem. 2010;285:12299–307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Kikuchi S, Hara K, Shimizu T, Sato M, Hashimoto H. Structural basis of recruitment of DNA polymerase zeta by interaction between REV1 and REV7 proteins. J Biol Chem. 2012;287:33847–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Masuda Y, Ohmae M, Masuda K, Kamiya K. Structure and enzymatic properties of a stable complex of the human REV1 and REV7 proteins. J Biol Chem. 2003;278:12356–60.

    Article  CAS  PubMed  Google Scholar 

  126. Murakumo Y, Ogura Y, Ishii H, Numata S, Ichihara M, Croce CM, Fishel R, Takahashi M. Interactions in the error-prone postreplication repair proteins hREV1, hREV3, and hREV7. J Biol Chem. 2001;276:35644–51.

    Article  CAS  PubMed  Google Scholar 

  127. Ohashi E, Hanafusa T, Kamei K, Song I, Tomida J, Hashimoto H, Vaziri C, Ohmori H. Identification of a novel REV1-interacting motif necessary for DNA polymerase kappa function. Genes Cells. 2009;14:101–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Ohashi E, Murakumo Y, Kanjo N, Akagi J, Masutani C, Hanaoka F, Ohmori H. Interaction of hREV1 with three human Y-family DNA polymerases. Genes Cells. 2004;9:523–31.

    Article  CAS  PubMed  Google Scholar 

  129. Tissier A, Kannouche P, Reck MP, Lehmann AR, Fuchs RP, Cordonnier A. Co-localization in replication foci and interaction of human Y-family members, DNA polymerase pol eta and REVl protein. DNA Repair (Amst). 2004;3:1503–14.

    Article  CAS  Google Scholar 

  130. Ohmori H, Hanafusa T, Ohashi E, Vaziri C. Separate roles of structured and unstructured regions of Y-family DNA polymerases. Adv Protein Chem Struct Biol. 2009;78:99–146.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Akagi J, Masutani C, Kataoka Y, Kan T, Ohashi E, Mori T, Ohmori H, Hanaoka F. Interaction with DNA polymerase eta is required for nuclear accumulation of REV1 and suppression of spontaneous mutations in human cells. DNA Repair (Amst). 2009;8:585–99.

    Article  CAS  Google Scholar 

  132. Boehm EM, Powers KT, Kondratick CM, Spies M, Houtman JC, Washington MT. The proliferating cell nuclear antigen (PCNA)-interacting protein (PIP) motif of DNA polymerase eta mediates its interaction with the C-terminal domain of Rev1. J Biol Chem. 2016;291:8735–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Yoon JH, Park J, Conde J, Wakamiya M, Prakash L, Prakash S. Rev1 promotes replication through UV lesions in conjunction with DNA polymerases eta, iota, and kappa but not DNA polymerase zeta. Genes Dev. 2015;29:2588–602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Gibbs PE, McGregor WG, Maher VM, Nisson P, Lawrence CW. A human homolog of the Saccharomyces cerevisiae REV3 gene, which encodes the catalytic subunit of DNA polymerase zeta. Proc Natl Acad Sci U S A. 1998;95:6876–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Murakumo Y, Roth T, Ishii H, Rasio D, Numata S, Croce CM, Fishel R. A human REV7 homolog that interacts with the polymerase zeta catalytic subunit hREV3 and the spindle assembly checkpoint protein hMAD2. J Biol Chem. 2000;275:4391–7.

    Article  CAS  PubMed  Google Scholar 

  136. Van Sloun PP, Romeijn RJ, Eeken JC. Molecular cloning, expression and chromosomal localisation of the mouse Rev3l gene, encoding the catalytic subunit of polymerase zeta. Mutat Res. 1999;433:109–16.

    Article  PubMed  Google Scholar 

  137. Yu Y, Yang J, Zhu F, Xu F. Response of REV3 promoter to N-methyl-N′-nitro-N-nitrosoguanidine. Mutat Res. 2004;550:49–58.

    Article  CAS  PubMed  Google Scholar 

  138. Diaz M, Watson NB, Turkington G, Verkoczy LK, Klinman NR, McGregor WG. Decreased frequency and highly aberrant spectrum of ultraviolet-induced mutations in the hprt gene of mouse fibroblasts expressing antisense RNA to DNA polymerase zeta. Mol Cancer Res. 2003;1:836–47.

    CAS  PubMed  Google Scholar 

  139. Li Z, Zhang H, McManus TP, McCormick JJ, Lawrence CW, Maher VM. hREV3 is essential for error-prone translesion synthesis past UV or benzo[a]pyrene diol epoxide-induced DNA lesions in human fibroblasts. Mutat Res. 2002;510:71–80.

    Article  CAS  PubMed  Google Scholar 

  140. Wu F, Lin X, Okuda T, Howell SB. DNA polymerase zeta regulates cisplatin cytotoxicity, mutagenicity, and the rate of development of cisplatin resistance. Cancer Res. 2004;64:8029–35.

    Article  CAS  PubMed  Google Scholar 

  141. Bemark M, Khamlichi AA, Davies SL, Neuberger MS. Disruption of mouse polymerase zeta (Rev3) leads to embryonic lethality and impairs blastocyst development in vitro. Curr Biol. 2000;10:1213–6.

    Article  CAS  PubMed  Google Scholar 

  142. Esposito G, Godindagger I, Klein U, Yaspo ML, Cumano A, Rajewsky K. Disruption of the Rev3l-encoded catalytic subunit of polymerase zeta in mice results in early embryonic lethality. Curr Biol. 2000;10:1221–4.

    Article  CAS  PubMed  Google Scholar 

  143. O-Wang J, Kajiwara K, Kawamura K, Kimura M, Miyagishima H, Koseki H, Tagawa M. An essential role for REV3 in mammalian cell survival: absence of REV3 induces p53-independent embryonic death. Biochem Biophys Res Commun. 2002;293:1132–7.

    Article  CAS  PubMed  Google Scholar 

  144. Van Sloun PP, Varlet I, Sonneveld E, Boei JJ, Romeijn RJ, Eeken JC, De Wind N. Involvement of mouse Rev3 in tolerance of endogenous and exogenous DNA damage. Mol Cell Biol. 2002;22:2159–69.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  145. Wittschieben J, Shivji MK, Lalani E, Jacobs MA, Marini F, Gearhart PJ, Rosewell I, Stamp G, Wood RD. Disruption of the developmentally regulated Rev3l gene causes embryonic lethality. Curr Biol. 2000;10:1217–20.

    Article  CAS  PubMed  Google Scholar 

  146. Jansen JG, Tsaalbi-Shtylik A, Hendriks G, Verspuy J, Gali H, Haracska L, de Wind N. Mammalian polymerase zeta is essential for post-replication repair of UV-induced DNA lesions. DNA Repair (Amst). 2009;8:1444–51.

    Article  CAS  Google Scholar 

  147. Wittschieben JP, Reshmi SC, Gollin SM, Wood RD. Loss of DNA polymerase zeta causes chromosomal instability in mammalian cells. Cancer Res. 2006;66:134–42.

    Article  CAS  PubMed  Google Scholar 

  148. Wittschieben JP, Patil V, Glushets V, Robinson LJ, Kusewitt DF, Wood RD. Loss of DNA polymerase zeta enhances spontaneous tumorigenesis. Cancer Res. 2010;70:2770–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Cheung HW, Chun AC, Wang Q, Deng W, Hu L, Guan XY, Nicholls JM, Ling MT, Chuan Wong Y, Tsao SW, et al. Inactivation of human MAD2B in nasopharyngeal carcinoma cells leads to chemosensitization to DNA-damaging agents. Cancer Res. 2006;66:4357–67.

    Article  CAS  PubMed  Google Scholar 

  150. McNally K, Neal JA, McManus TP, McCormick JJ, Maher VM. hRev7, putative subunit of hPolzeta, plays a critical role in survival, induction of mutations, and progression through S-phase, of UV((254nm))-irradiated human fibroblasts. DNA Repair (Amst). 2008;7:597–604.

    Article  CAS  Google Scholar 

  151. Watanabe N, Mii S, Asai N, Asai M, Niimi K, Ushida K, Kato T, Enomoto A, Ishii H, Takahashi M, et al. The REV7 subunit of DNA polymerase zeta is essential for primordial germ cell maintenance in the mouse. J Biol Chem. 2013;288:10459–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Tomida J, Takata K, Lange SS, Schibler AC, Yousefzadeh MJ, Bhetawal S, Dent SY, Wood RD. REV7 is essential for DNA damage tolerance via two REV3L binding sites in mammalian DNA polymerase zeta. Nucleic Acids Res. 2015;43:1000–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Boersma V, Moatti N, Segura-Bayona S, Peuscher MH, van der Torre J, Wevers BA, Orthwein A, Durocher D, Jacobs JJ. MAD2L2 controls DNA repair at telomeres and DNA breaks by inhibiting 5′ end resection. Nature. 2015;521:537–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Xu G, Chapman JR, Brandsma I, Yuan J, Mistrik M, Bouwman P, Bartkova J, Gogola E, Warmerdam D, Barazas M, et al. REV7 counteracts DNA double-strand break resection and affects PARP inhibition. Nature. 2015;521:541–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Bluteau D, Masliah-Planchon J, Clairmont C, Rousseau A, Ceccaldi R, Dubois d’Enghien C, Bluteau O, Cuccuini W, Gachet S, Peffault de Latour R, et al. Biallelic inactivation of REV7 is associated with Fanconi anemia. J Clin Invest. 2016;126:3580–4.

    Article  PubMed  PubMed Central  Google Scholar 

  156. Marini F, Kim N, Schuffert A, Wood RD. POLN, a nuclear PolA family DNA polymerase homologous to the DNA cross-link sensitivity protein Mus308. J Biol Chem. 2003;278:32014–9.

    Article  CAS  PubMed  Google Scholar 

  157. Seki M, Marini F, Wood RD. POLQ (Pol theta), a DNA polymerase and DNA-dependent ATPase in human cells. Nucleic Acids Res. 2003;31:6117–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Sharief FS, Vojta PJ, Ropp PA, Copeland WC. Cloning and chromosomal mapping of the human DNA polymerase theta (POLQ), the eighth human DNA polymerase. Genomics. 1999;59:90–6.

    Article  CAS  PubMed  Google Scholar 

  159. Seki M, Masutani C, Yang LW, Schuffert A, Iwai S, Bahar I, Wood RD. High-efficiency bypass of DNA damage by human DNA polymerase Q. EMBO J. 2004;23:4484–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Takata K, Shimizu T, Iwai S, Wood RD. Human DNA polymerase N (POLN) is a low fidelity enzyme capable of error-free bypass of 5S-thymine glycol. J Biol Chem. 2006;281:23445–55.

    Article  CAS  PubMed  Google Scholar 

  161. Zietlow L, Smith LA, Bessho M, Bessho T. Evidence for the involvement of human DNA polymerase N in the repair of DNA interstrand cross-links. Biochemistry. 2009;48:11817–24.

    Article  CAS  PubMed  Google Scholar 

  162. Seki M, Wood RD. DNA polymerase theta (POLQ) can extend from mismatches and from bases opposite a (6-4) photoproduct. DNA Repair (Amst). 2008;7:119–27.

    Article  CAS  Google Scholar 

  163. Shima N, Hartford SA, Duffy T, Wilson LA, Schimenti KJ, Schimenti JC. Phenotype-based identification of mouse chromosome instability mutants. Genetics. 2003;163:1031–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  164. Shima N, Munroe RJ, Schimenti JC. The mouse genomic instability mutation chaos1 is an allele of Polq that exhibits genetic interaction with Atm. Mol Cell Biol. 2004;24:10381–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Goff JP, Shields DS, Seki M, Choi S, Epperly MW, Dixon T, Wang H, Bakkenist CJ, Dertinger SD, Torous DK, et al. Lack of DNA polymerase theta (POLQ) radiosensitizes bone marrow stromal cells in vitro and increases reticulocyte micronuclei after total-body irradiation. Radiat Res. 2009;172:165–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Li Y, Gao X, Wang JY. Comparison of two POLQ mutants reveals that a polymerase-inactive POLQ retains significant function in tolerance to etoposide and gamma-irradiation in mouse B cells. Genes Cells. 2011;16:973–83.

    CAS  PubMed  Google Scholar 

  167. Ceccaldi R, Liu JC, Amunugama R, Hajdu I, Primack B, Petalcorin MI, O’Connor KW, Konstantinopoulos PA, Elledge SJ, Boulton SJ, et al. Homologous-recombination-deficient tumours are dependent on Poltheta-mediated repair. Nature. 2015;518:258–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Mateos-Gomez PA, Gong F, Nair N, Miller KM, Lazzerini-Denchi E, Sfeir A. Mammalian polymerase theta promotes alternative NHEJ and suppresses recombination. Nature. 2015;518:254–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Wyatt DW, Feng W, Conlin MP, Yousefzadeh MJ, Roberts SA, Mieczkowski P, Wood RD, Gupta GP, Ramsden DA. Essential roles for polymerase theta-mediated end joining in the repair of chromosome breaks. Mol Cell. 2016;63:662–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Zahn KE, Averill AM, Aller P, Wood RD, Doublie S. Human DNA polymerase theta grasps the primer terminus to mediate DNA repair. Nat Struct Mol Biol. 2015;22:304–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Moldovan GL, Madhavan MV, Mirchandani KD, McCaffrey RM, Vinciguerra P, D’Andrea AD. DNA polymerase POLN participates in cross-link repair and homologous recombination. Mol Cell Biol. 2010;30:1088–96.

    Article  CAS  PubMed  Google Scholar 

  172. Lee YS, Gao Y, Yang W. How a homolog of high-fidelity replicases conducts mutagenic DNA synthesis. Nat Struct Mol Biol. 2015;22:298–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Garcia-Gomez S, Reyes A, Martinez-Jimenez MI, Chocron ES, Mouron S, Terrados G, Powell C, Salido E, Mendez J, Holt IJ, et al. PrimPol, an archaic primase/polymerase operating in human cells. Mol Cell. 2013;52:541–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Mouron S, Rodriguez-Acebes S, Martinez-Jimenez MI, Garcia-Gomez S, Chocron S, Blanco L, Mendez J. Repriming of DNA synthesis at stalled replication forks by human PrimPol. Nat Struct Mol Biol. 2013;20:1383–9.

    Article  CAS  PubMed  Google Scholar 

  175. Schiavone D, Jozwiakowski SK, Romanello M, Guilbaud G, Guilliam TA, Bailey LJ, Sale JE, Doherty AJ. PrimPol is required for replicative tolerance of G Quadruplexes in vertebrate cells. Mol Cell. 2016;61:161–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Kobayashi K, Guilliam TA, Tsuda M, Yamamoto J, Bailey LJ, Iwai S, Takeda S, Doherty AJ, Hirota K. Repriming by PrimPol is critical for DNA replication restart downstream of lesions and chain-terminating nucleosides. Cell Cycle. 2016;15:1997–2008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Bianchi J, Rudd SG, Jozwiakowski SK, Bailey LJ, Soura V, Taylor E, Stevanovic I, Green AJ, Stracker TH, Lindsay HD, et al. PrimPol bypasses UV photoproducts during eukaryotic chromosomal DNA replication. Mol Cell. 2013;52:566–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Zafar MK, Ketkar A, Lodeiro MF, Cameron CE, Eoff RL. Kinetic analysis of human PrimPol DNA polymerase activity reveals a generally error-prone enzyme capable of accurately bypassing 7,8-dihydro-8-oxo-2′-deoxyguanosine. Biochemistry. 2014;53:6584–94.

    Article  CAS  PubMed  Google Scholar 

  179. Martinez-Jimenez MI, Garcia-Gomez S, Bebenek K, Sastre-Moreno G, Calvo PA, Diaz-Talavera A, Kunkel TA, Blanco L. Alternative solutions and new scenarios for translesion DNA synthesis by human PrimPol. DNA Repair (Amst). 2015;29:127–38.

    Article  CAS  Google Scholar 

  180. Guilliam TA, Jozwiakowski SK, Ehlinger A, Barnes RP, Rudd SG, Bailey LJ, Skehel JM, Eckert KA, Chazin WJ, Doherty AJ. Human PrimPol is a highly error-prone polymerase regulated by single-stranded DNA binding proteins. Nucleic Acids Res. 2015;43:1056–68.

    Article  CAS  PubMed  Google Scholar 

  181. Wan L, Lou J, Xia Y, Su B, Liu T, Cui J, Sun Y, Lou H, Huang J. hPrimpol1/CCDC111 is a human DNA primase-polymerase required for the maintenance of genome integrity. EMBO Rep. 2013;14:1104–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Zhao F, Wu J, Xue A, Su Y, Wang X, Lu X, Zhou Z, Qu J, Zhou X. Exome sequencing reveals CCDC111 mutation associated with high myopia. Hum Genet. 2013;132:913–21.

    Article  CAS  PubMed  Google Scholar 

  183. Keen BA, Jozwiakowski SK, Bailey LJ, Bianchi J, Doherty AJ. Molecular dissection of the domain architecture and catalytic activities of human PrimPol. Nucleic Acids Res. 2014;42:5830–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and by Takeda Science Foundation.

Author information

Authors and Affiliations

  1. Department of Genome Dynamics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan

    Chikahide Masutani

  2. Department of Life Science, Graduate School of Science, Gakushuin University, Tokyo, Japan

    Fumio Hanaoka

  3. Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba-shi, Ibaraki, Japan

    Fumio Hanaoka

Authors
  1. Chikahide Masutani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fumio Hanaoka
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chikahide Masutani .

Editor information

Editors and Affiliations

  1. Department of Dermatology, Graduate School of Medicine, Kobe University, Kobe, Japan

    Chikako Nishigori

  2. Biosignal Research Center, Kobe University, Kobe, Japan

    Kaoru Sugasawa

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Masutani, C., Hanaoka, F. (2019). Translesion DNA Synthesis. In: Nishigori, C., Sugasawa, K. (eds) DNA Repair Disorders. Springer, Singapore. https://doi.org/10.1007/978-981-10-6722-8_12

Download citation

  • DOI: https://doi.org/10.1007/978-981-10-6722-8_12

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-10-6721-1

  • Online ISBN: 978-981-10-6722-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation