1932

Abstract

Replicative polymerases (pols) cannot accommodate damaged template bases, and these pols stall when such offenses are encountered during S phase. Rather than repairing the damaged base, replication past it may proceed via one of two DNA damage tolerance (DDT) pathways, allowing replicative DNA synthesis to resume. In translesion DNA synthesis (TLS), a specialized TLS pol is recruited to catalyze stable, yet often erroneous, nucleotide incorporation opposite damaged template bases. In template switching, the newly synthesized sister strand is used as a damage-free template to synthesize past the lesion. In eukaryotes, both pathways are regulated by the conjugation of ubiquitin to the PCNA sliding clamp by distinct E2/E3 pairs. Whereas monoubiquitination by Rad6/Rad18 mediates TLS, extension of this ubiquitin to a polyubiquitin chain by Ubc13–Mms2/Rad5 routes DDT to the template switching pathway. In this review, we focus on the monoubiquitination of PCNA by Rad6/Rad18 and summarize the current knowledge of how this process is regulated.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-biophys-060414-033841
2015-06-22
2024-06-16
Loading full text...

Full text loading...

/deliver/fulltext/biophys/44/1/annurev-biophys-060414-033841.html?itemId=/content/journals/10.1146/annurev-biophys-060414-033841&mimeType=html&fmt=ahah

Literature Cited

  1. Andersen PL, Xu F, Xiao W. 1.  2008. Eukaryotic DNA damage tolerance and translesion synthesis through covalent modifications of PCNA. Cell Res. 18:162–73 [Google Scholar]
  2. Armstrong AA, Mohideen F, Lima CD. 2.  2012. Recognition of SUMO-modified PCNA requires tandem receptor motifs in Srs2. Nature 483:59–63 [Google Scholar]
  3. Avkin S, Goldsmith M, Velasco-Miguel S, Geacintov N, Friedberg EC, Livneh Z. 3.  2004. Quantitative analysis of translesion DNA synthesis across a benzo[a]pyrene-guanine adduct in mammalian cells: the role of DNA polymerase κ. J. Biol. Chem. 279:53298–305 [Google Scholar]
  4. Bailly V, Lamb J, Sung P, Prakash S, Prakash L. 4.  1994. Specific complex formation between yeast RAD6 and RAD18 proteins: a potential mechanism for targeting RAD6 ubiquitin-conjugating activity to DNA damage sites. Genes Dev. 8:811–20 [Google Scholar]
  5. Bailly V, Lauder S, Prakash S, Prakash L. 5.  1997. Yeast DNA repair proteins Rad6 and Rad18 form a heterodimer that has ubiquitin conjugating, DNA binding, and ATP hydrolytic activities. J. Biol. Chem. 272:23360–365 [Google Scholar]
  6. Bailly V, Prakash S, Prakash L. 6.  1997. Domains required for dimerization of yeast Rad6 ubiquitin-conjugating enzyme and Rad18 DNA binding protein. Mol. Cell. Biol. 17:4536–43 [Google Scholar]
  7. Balakrishnan L, Bambara RA. 7.  2011. Eukaryotic lagging strand DNA replication employs a multi-pathway mechanism that protects genome integrity. J. Biol. Chem. 286:6865–70 [Google Scholar]
  8. Barber LJ, Youds JL, Ward JD, McIlwraith MJ, O'Neil NJ. 8.  et al. 2008. RTEL1 maintains genomic stability by suppressing homologous recombination. Cell 135:261–71 [Google Scholar]
  9. Barkley LR, Palle K, Durando M, Day TA, Gurkar A. 9.  et al. 2012. c-Jun N-terminal kinase-mediated Rad18 phosphorylation facilitates Polη recruitment to stalled replication forks. Mol. Biol. Cell 23:1943–54 [Google Scholar]
  10. Beukers R, Eker APM, Lohman PHM. 10.  2008. 50 years thymine dimer. DNA Repair 7:530–43 [Google Scholar]
  11. Bi X, Barkley LR, Slater DM, Tateishi S, Yamaizumi M. 11.  et al. 2006. Rad18 regulates DNA polymerase κ and is required for recovery from S-phase checkpoint-mediated arrest. Mol. Cell. Biol. 26:3527–40 [Google Scholar]
  12. Boos D, Frigola J, Diffley JFX. 12.  2012. Activation of the replicative DNA helicase: Breaking up is hard to do. Curr. Opin. Cell Biol. 24:423–30 [Google Scholar]
  13. Branzei D, Vanoli F, Foiani M. 13.  2008. SUMOylation regulates Rad18-mediated template switch. Nature 456:915–20 [Google Scholar]
  14. Brun J, Chiu RK, Wouters BG, Gray DA. 14.  2010. Regulation of PCNA polyubiquitination in human cells. BMC Res. Notes 3:85 [Google Scholar]
  15. Bruning JB, Shamoo Y. 15.  2004. Structural and thermodynamic analysis of human PCNA with peptides derived from DNA polymerase-δ p66 subunit and flap endonuclease-1. Structure 12:2209–19 [Google Scholar]
  16. Burkovics P, Sebesta M, Sisakova A, Plault N, Szukacsov V. 16.  et al. 2013. Srs2 mediates PCNA-SUMO-dependent inhibition of DNA repair synthesis. EMBO J. 32:742–55 [Google Scholar]
  17. Byun TS, Pacek M, Yee MC, Walter JC, Cimprich KA. 17.  2005. Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint. Genes Dev. 19:1040–52 [Google Scholar]
  18. Centore RC, Yazinski SA, Tse A, Zou L. 18.  2012. Spartan/C1orf124, a reader of PCNA ubiquitylation and a regulator of UV-induced DNA damage response. Mol. Cell 46:625–35 [Google Scholar]
  19. Chang DJ, Lupardus PJ, Cimprich KA. 19.  2006. Monoubiquitination of proliferating cell nuclear antigen induced by stalled replication requires uncoupling of DNA polymerase and mini-chromosome maintenance helicase activities. J. Biol. Chem. 281:32081–88 [Google Scholar]
  20. Chiapperino D, Kroth H, Kramarczuk IH, Sayer JM, Masutani C. 20.  et al. 2002. Preferential misincorporation of purine nucleotides by human DNA polymerase η opposite benzo[a]pyrene 7,8-diol 9,10-epoxide deoxyguanosine adducts. J. Biol. Chem. 277:11765–71 [Google Scholar]
  21. Chun ACS, Jin D-Y. 21.  2010. Ubiquitin-dependent regulation of translesion polymerases. Biochem. Soc. Trans. 38:110–15 [Google Scholar]
  22. Daigaku Y, Davies AA, Ulrich HD. 22.  2010. Ubiquitin-dependent DNA damage bypass is separable from genome replication. Nature 465:951–55 [Google Scholar]
  23. Davies AA, Huttner D, Daigaku Y, Chen S, Ulrich HD. 23.  2008. Activation of ubiquitin-dependent DNA damage bypass is mediated by replication protein A. Mol. Cell 29:625–36 [Google Scholar]
  24. Davis EJ, Lachaud C, Appleton P, Macartney TJ, Nathke I, Rouse J. 24.  2012. DVC1 (C1orf124) recruits the p97 protein segregase to sites of DNA damage. Nat. Struct. Mol. Biol. 19:1093–100 [Google Scholar]
  25. Day TA, Palle K, Barkley LR, Kakusho N, Zou Y. 25.  et al. 2010. Phosphorylated Rad18 directs DNA polymerase η to sites of stalled replication. J. Cell Biol. 191:953–66 [Google Scholar]
  26. Durando M, Tateishi S, Vaziri C. 26.  2013. A non-catalytic role of DNA polymerase η in recruiting Rad18 and promoting PCNA monoubiquitination at stalled replication forks. Nucleic Acids Res. 41:3079–93 [Google Scholar]
  27. Emanuele MJ, Ciccia A, Elia AEH, Elledge SJ. 27.  2011. Proliferating cell nuclear antigen (PCNA)-associated KIAA0101/PAF15 protein is a cell cycle-regulated anaphase-promoting complex/cyclosome substrate. PNAS 108:9845–50 [Google Scholar]
  28. Falbo KB, Alabert C, Katou Y, Wu S, Han J. 28.  et al. 2009. Involvement of a chromatin remodeling complex in damage tolerance during DNA replication. Nat. Struct. Mol. Biol. 16:1167–72 [Google Scholar]
  29. Finley D, Ulrich HD, Sommer T, Kaiser P. 29.  2012. The ubiquitin-proteasome system of Saccharomyces cerevisiae. Genetics 192:319–60 [Google Scholar]
  30. Flotho A, Melchior F. 30.  2013. Sumoylation: a regulatory protein modification in health and disease. Annu. Rev. Biochem. 82:357–85 [Google Scholar]
  31. Frampton J, Irmisch A, Green CM, Neiss A, Trickey M. 31.  et al. 2006. Postreplication repair and PCNA modification in Schizosaccharomyces pombe. Mol. Biol. Cell 17:2976–85 [Google Scholar]
  32. Freudenthal BD, Gakhar L, Ramaswamy S, Washington MT. 32.  2010. Structure of monoubiquitinated PCNA and implications for translesion synthesis and DNA polymerase exchange. Nat. Struct. Mol. Biol. 17:479–84 [Google Scholar]
  33. Frick DN, Richardson CC. 33.  2001. DNA primases. Annu. Rev. Biochem. 70:39–80 [Google Scholar]
  34. Friedberg EC. 34.  2005. Suffering in silence: the tolerance of DNA damage. Nat. Rev. Mol. Cell Biol. 6:943–53 [Google Scholar]
  35. Fugger K, Mistrik M, Danielsen JR, Dinant C, Falck J. 35.  et al. 2009. Human Fbh1 helicase contributes to genome maintenance via pro- and anti-recombinase activities. J. Cell Biol. 186:655–63 [Google Scholar]
  36. Gali H, Juhasz S, Morocz M, Hajdu I, Fatyol K. 36.  et al. 2012. Role of SUMO modification of human PCNA at stalled replication fork. Nucleic Acids Res. 40:6049–59 [Google Scholar]
  37. Garg P, Burgers PM. 37.  2005. Ubiquitinated proliferating cell nuclear antigen activates translesion DNA polymerases η and REV1. PNAS 102:18361–66 [Google Scholar]
  38. Georgescu RE, Langston L, Yao NY, Yurieva O, Zhang D. 38.  et al. 2014. Mechanism of asymmetric polymerase assembly at the eukaryotic replication fork. Nat. Struct. Mol. Biol. 21:664–70 [Google Scholar]
  39. Ghosal G, Leung JW-C, Nair BC, Fong K-W, Chen J. 39.  2012. Proliferating cell nuclear antigen (PCNA)-binding protein C1orf124 is a regulator of translesion synthesis. J. Biol. Chem. 287:34225–33 [Google Scholar]
  40. Gohler T, Munoz IM, Rouse J, Blow JJ. 40.  2008. PTIP/Swift is required for efficient PCNA ubiquitination in response to DNA damage. DNA Repair 7:775–87 [Google Scholar]
  41. Goodarzi AA, Kurka T, Jeggo PA. 41.  2011. KAP-1 phosphorylation regulates CHD3 nucleosome remodeling during the DNA double-strand break response. Nat. Struct. Mol. Biol. 18:831–39 [Google Scholar]
  42. Han J, Liu T, Huen MSY, Hu L, Chen Z, Huang J. 42.  2014. SIVA1 directs the E3 ubiquitin ligase RAD18 for PCNA monoubiquitination. J. Cell Biol. 205:811–27 [Google Scholar]
  43. Haracska L, Torres-Ramos CA, Johnson RE, Prakash S, Prakash L. 43.  2004. Opposing effects of ubiquitin conjugation and SUMO modification of PCNA on replicational bypass of DNA lesions in Saccharomyces cerevisiae. Mol. Cell. Biol. 24:4267–74 [Google Scholar]
  44. Haracska L, Unk I, Prakash L, Prakash S. 44.  2006. Ubiquitylation of yeast proliferating cell nuclear antigen and its implications for translesion DNA synthesis. PNAS 103:6477–82 [Google Scholar]
  45. Hedglin M, Kumar R, Benkovic SJ. 45.  2013. Replication clamps and clamp loaders. Cold Spring Harb. Perspect. Biol. 5:a010165 [Google Scholar]
  46. Hibbert RG, Huang A, Boelens R, Sixma TK. 46.  2011. E3 ligase Rad18 promotes monoubiquitination rather than ubiquitin chain formation by E2 enzyme Rad6. PNAS 108:5590–95 [Google Scholar]
  47. Hoege C, Pfander B, Moldovan GL, Pyrowolakis G, Jentsch S. 47.  2002. RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO. Nature 419:135–41 [Google Scholar]
  48. Hosokawa M, Takehara A, Matsuda K, Eguchi H, Ohigashi H. 48.  et al. 2007. Oncogenic role of KIAA0101 interacting with proliferating cell nuclear antigen in pancreatic cancer. Cancer Res. 67:2568–76 [Google Scholar]
  49. Hu Y, Raynard S, Sehorn MG, Lu X, Bussen W. 49.  et al. 2007. RECQL5/Recql5 helicase regulates homologous recombination and suppresses tumor formation via disruption of Rad51 presynaptic filaments. Genes Dev. 21:3073–84 [Google Scholar]
  50. Huang A, Hibbert RG, de Jong RN, Das D, Sixma TK, Boelens R. 50.  2011. Symmetry and asymmetry of the RING–RING dimer of Rad18. J. Mol. Biol. 410:424–35 [Google Scholar]
  51. Huang J, Huen MSY, Kim H, Leung CCY, Glover JNM. 51.  et al. 2009. RAD18 transmits DNA damage signalling to elicit homologous recombination repair. Nat. Cell Biol. 11:592–603 [Google Scholar]
  52. Johnson RE, Haracska L, Prakash S, Prakash L. 52.  2001. Role of DNA polymerase η in the bypass of a (6-4) TT photoproduct. Mol. Cell. Biol. 21:3558–63 [Google Scholar]
  53. Jones JS, Prakash L. 53.  1991. Transcript levels of the Saccharomyces cerevisiae DNA repair gene RAD18 increase in UV irradiated cells and during meiosis but not during the mitotic cell cycle. Nucleic Acids Res. 19:893–98 [Google Scholar]
  54. Jones JS, Weber S, Prakash L. 54.  1988. The Saccharomyces cerevisiae RAD18 gene encodes a protein that contains potential zinc finger domains for nucleic acid binding and a putative nucleotide binding sequence. Nucleic Acids Res. 16:7119–31 [Google Scholar]
  55. Juhasz S, Balogh D, Hajdu I, Burkovics P, Villamil MA. 55.  et al. 2012. Characterization of human Spartan/C1orf124, an ubiquitin-PCNA interacting regulator of DNA damage tolerance. Nucleic Acids Res. 40:10795–808 [Google Scholar]
  56. Kannouche PL, Wing J, Lehmann AR. 56.  2004. Interaction of human DNA polymerase η with monoubiquitinated PCNA: a possible mechanism for the polymerase switch in response to DNA damage. Mol. Cell 14:491–500 [Google Scholar]
  57. Kim H, Dejsuphong D, Adelmant G, Ceccaldi R, Yang K. 57.  et al. 2014. Transcriptional repressor ZBTB1 promotes chromatin remodeling and translesion DNA synthesis. Mol. Cell 54:107–18 [Google Scholar]
  58. Kim MS, Machida Y, Vashisht AA, Wohlschlegel JA, Pang Y-P, Machida YJ. 58.  2013. Regulation of error-prone translesion synthesis by Spartan/C1orf124. Nucleic Acids Res. 41:1661–68 [Google Scholar]
  59. Klarer AC, Stallons LJ, Burke TJ, Skaggs RL, McGregor WG. 59.  2012. DNA polymerase eta participates in the mutagenic bypass of adducts induced by benzo[a]pyrene diol epoxide in mammalian cells. PLOS ONE 7:e39596 [Google Scholar]
  60. Koken M, Reynolds P, Bootsma D, Hoeijmakers J, Prakash S, Prakash L. 60.  1991. Dhr6, a Drosophila homolog of the yeast DNA-repair gene RAD6. PNAS 88:3832–36 [Google Scholar]
  61. Krejci L, Altmannova V, Spirek M, Zhao X. 61.  2012. Homologous recombination and its regulation. Nucleic Acids Res. 40:5795–818 [Google Scholar]
  62. Krejci L, Van Komen S, Li Y, Villemain J, Reddy MS. 62.  et al. 2003. DNA helicase Srs2 disrupts the Rad51 presynaptic filament. Nature 423:305–09 [Google Scholar]
  63. Kuchta RD, Stengel G. 63.  2010. Mechanism and evolution of DNA primases. Biochim. Biophys. Acta 1804:1180–89 [Google Scholar]
  64. Lange SS, Takata K, Wood RD. 64.  2011. DNA polymerases and cancer. Nat. Rev. 11:96–110 [Google Scholar]
  65. Lehmann AR. 65.  2005. Replication of damaged DNA by translesion synthesis in human cells. FEBS Lett. 579:873–76 [Google Scholar]
  66. Lehmann AR, Niimi A, Ogi T, Brown S, Sabbioneda S. 66.  et al. 2007. Translesion synthesis: Y-family polymerases and the polymerase switch. DNA Repair 6:891–99 [Google Scholar]
  67. Liberi G, Maffioletti G, Lucca C, Chiolo I, Baryshnikova A. 67.  et al. 2005. Rad51-dependent DNA structures accumulate at damaged replication forks in sgs1 mutants defective in the yeast ortholog of BLM RecQ helicase. Genes Dev. 19:339–50 [Google Scholar]
  68. Lin JR, Zeman MK, Chen JY, Yee MC, Cimprich KA. 68.  2011. SHPRH and HLTF act in a damage-specific manner to coordinate different forms of postreplication repair and prevent mutagenesis. Mol. Cell 42:237–49 [Google Scholar]
  69. Liu G, Chen X. 69.  2006. DNA polymerase η, the product of the xeroderma pigmentosum variant gene and a target of p53, modulates the DNA damage checkpoint and p53 activation. Mol. Cell. Biol. 26:1398–413 [Google Scholar]
  70. Liu Y, Yang Y, Tang T-S, Zhang H, Wang Z. 70.  et al. 2014. Variants of mouse DNA polymerase κ reveal a mechanism of efficient and accurate translesion synthesis past a benzo[a]pyrene dG adduct. PNAS 111:1789–94 [Google Scholar]
  71. Logette E, Schuepbach-Mallepell S, Eckert MJ, Leo XH, Jaccard B. 71.  et al. 2011. PIDD orchestrates translesion DNA synthesis in response to UV irradiation. Cell Death Differ. 18:1036–45 [Google Scholar]
  72. Lyakhovich A, Shekhar MPV. 72.  2003. Supramolecular complex formation between Rad6 and proteins of the p53 pathway during DNA damage-induced response. Mol. Cell. Biol. 23:2463–75 [Google Scholar]
  73. Lyakhovich A, Shekhar MPV. 73.  2004. RAD6B overexpression confers chemoresistance: RAD6 expression during cell cycle and its redistribution to chromatin during DNA damage-induced response. Oncogene 23:3097–106 [Google Scholar]
  74. Machida Y, Kim MS, Machida YJ. 74.  2012. Spartan/C1orf124 is important to prevent UV-induced mutagenesis. Cell Cycle 11:3395–402 [Google Scholar]
  75. Madura K, Prakash S, Prakash L. 75.  1990. Expression of the Saccharomyces cerevisiae DNA repair gene RAD6 that encodes a ubiquitin conjugating enzyme, increases in response to DNA damage and in meiosis but remains constant during the mitotic cell cycle. Nucleic Acids Res. 18:771–78 [Google Scholar]
  76. Mansilla SF, Soria G, Vallerga MB, Habif M, Martínez-López W. 76.  et al. 2013. UV-triggered p21 degradation facilitates damaged-DNA replication and preserves genomic stability. Nucleic Acids Res. 41:6942–51 [Google Scholar]
  77. Masuda Y, Suzuki M, Kawai H, Suzuki F, Kamiya K. 77.  2012. Asymmetric nature of two subunits of RAD18, a RING-type ubiquitin ligase E3, in the human RAD6A-RAD18 ternary complex. Nucleic Acids Res. 40:1065–76 [Google Scholar]
  78. Masuyama S, Tateishi S, Yomogida K, Nishimune Y, Suzuki K. 78.  et al. 2005. Regulated expression and dynamic changes in subnuclear localization of mammalian Rad18 under normal and genotoxic conditions. Genes Cells 10:753–62 [Google Scholar]
  79. Mathiasen DP, Lisby M. 79.  2014. Cell cycle regulation of homologous recombination in Saccharomyces cerevisiae. FEMS Microbiol. Rev. 38:172–84 [Google Scholar]
  80. McGlynn P. 80.  2013. Helicases at the replication fork. Adv. Exp. Med. Biol. 767:97–121 [Google Scholar]
  81. Miyase S, Tateishi S, Watanabe K, Tomita K, Suzuki K. 81.  et al. 2005. Differential regulation of Rad18 through Rad6-dependent mono- and polyubiquitination. J. Biol. Chem. 280:515–24 [Google Scholar]
  82. Moldovan GL, Dejsuphong D, Petalcorin MI, Hofmann K, Takeda S. 82.  et al. 2012. Inhibition of homologous recombination by the PCNA-interacting protein PARI. Mol. Cell 45:75–86 [Google Scholar]
  83. Morrison AJ, Highland J, Krogan NJ, Arbel-Eden A, Greenblatt JF. 83.  et al. 2004. INO80 and γ-H2AX interaction links ATP-dependent chromatin remodeling to DNA damage repair. Cell 119:767–75 [Google Scholar]
  84. Mosbech A, Gibbs-Seymour I, Kagias K, Thorslund T, Beli P. 84.  et al. 2012. DVC1 (C1orf124) is a DNA damage–targeting p97 adaptor that promotes ubiquitin-dependent responses to replication blocks. Nat. Struct. Mol. Biol. 19:1084–92 [Google Scholar]
  85. Nakajima S, Lan L, Kanno S, Usami N, Kobayashi K. 85.  et al. 2006. Replication-dependent and -independent responses of RAD18 to DNA damage in human cells. J. Biol. Chem. 281:34687–95 [Google Scholar]
  86. Niimi A, Brown S, Sabbioneda S, Kannouche PL, Scott A. 86.  et al. 2008. Regulation of proliferating cell nuclear antigen ubiquitination in mammalian cells. PNAS 105:16125–30 [Google Scholar]
  87. Niimi A, Chambers AL, Downs JA, Lehmann AR. 87.  2012. A role for chromatin remodellers in replication of damaged DNA. Nucleic Acids Res. 40:7393–403 [Google Scholar]
  88. Nikiforov A, Svetlova M, Solovjeva L, Sasina L, Siino J. 88.  et al. 2004. DNA damage-induced accumulation of Rad18 protein at stalled replication forks in mammalian cells involves upstream protein phosphorylation. Biochem. Biophys. Res. Commun. 323:831–37 [Google Scholar]
  89. Nitani N, Yadani C, Yabuuchi H, Masukata H, Nakagawa T. 89.  2008. Mcm4 C-terminal domain of MCM helicase prevents excessive formation of single-stranded DNA at stalled replication forks. PNAS 105:12973–78 [Google Scholar]
  90. Notenboom V, Hibbert RG, van Rossum-Fikkert SE, Olsen JV, Mann M, Sixma TK. 90.  2007. Functional characterization of Rad18 domains for Rad6, ubiquitin, DNA binding and PCNA modification. Nucleic Acids Res. 35:5819–30 [Google Scholar]
  91. Ogi T, Shinkai Y, Tanaka K, Ohmori H. 91.  2002. Polκ protects mammalian cells against the lethal and mutagenic effects of benzo[a]pyrene. PNAS 99:15548–53 [Google Scholar]
  92. Papamichos-Chronakis M, Peterson CL. 92.  2008. The Ino80 chromatin-remodeling enzyme regulates replisome function and stability. Nat. Struct. Mol. Biol. 15:338–45 [Google Scholar]
  93. Papouli E, Chen S, Davies AA, Huttner D, Krejci L. 93.  et al. 2005. Crosstalk between SUMO and ubiquitin on PCNA is mediated by recruitment of the helicase Srs2p. Mol. Cell 19:123–33 [Google Scholar]
  94. Parker JL, Bucceri A, Davies AA, Heidrich K, Windecker H, Ulrich HD. 94.  2008. SUMO modification of PCNA is controlled by DNA. EMBO J. 27:2422–31 [Google Scholar]
  95. Parker JL, Ulrich HD. 95.  2009. Mechanistic analysis of PCNA poly-ubiquitylation by the ubiquitin protein ligases Rad18 and Rad5. EMBO J. 28:3657–66 [Google Scholar]
  96. Parker JL, Ulrich HD. 96.  2012. A SUMO-interacting motif activates budding yeast ubiquitin ligase Rad18 towards SUMO-modified PCNA. Nucleic Acids Res. 40:11380–88 [Google Scholar]
  97. Patel SS, Pandey M, Nandakumar D. 97.  2011. Dynamic coupling between the motors of DNA replication: hexameric helicase, DNA polymerase, and primase. Curr. Opin. Chem. Biol. 15:595–605 [Google Scholar]
  98. Pfander B, Moldovan GL, Sacher M, Hoege C, Jentsch S. 98.  2005. SUMO-modified PCNA recruits Srs2 to prevent recombination during S phase. Nature 436:428–33 [Google Scholar]
  99. Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB. 99.  et al. 2012. Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass. Nat. Cell Biol. 14:1089–98 [Google Scholar]
  100. Prakash S, Johnson RE, Prakash L. 100.  2005. Eukaryotic translesion synthesis DNA polymerases: specificity of structure and function. Annu. Rev. Biochem. 74:317–53 [Google Scholar]
  101. Prives C, Gottifredi V. 101.  2008. The p21 and PCNA partnership: a new twist for an old plot. Cell Cycle 7:3840–46 [Google Scholar]
  102. Rechkoblit O, Zhang Y, Guo D, Wang Z, Amin S. 102.  et al. 2002. trans-Lesion synthesis past bulky benzo[a]pyrene diol epoxide N2-dG and N6-dA lesions catalyzed by DNA bypass polymerases. J. Biol. Chem. 277:30488–94 [Google Scholar]
  103. Sale JE, Lehmann AR, Woodgate R. 103.  2012. Y-family DNA polymerases and their role in tolerance of cellular DNA damage. Nat. Rev. Mol. Cell Biol. 13:141–52 [Google Scholar]
  104. Sarcevic B, Mawson A, Baker RT, Sutherland RL. 104.  2002. Regulation of the ubiquitin-conjugating enzyme hHR6A by CDK-mediated phosphorylation. EMBO J. 21:2009–18 [Google Scholar]
  105. Schmutz V, Wagner J, Janel-Bintz R, Fuchs RPP, Cordonnier AM. 105.  2007. Requirements for PCNA monoubiquitination in human cell-free extracts. DNA Repair 6:1726–31 [Google Scholar]
  106. Schultz DC, Friedman JR, Rauscher FJ 3rd. 106.  2001. Targeting histone deacetylase complexes via KRAB-zinc finger proteins: the PHD and bromodomains of KAP-1 form a cooperative unit that recruits a novel isoform of the Mi-2α subunit of NuRD. Genes Dev. 15:428–43 [Google Scholar]
  107. Sertic S, Evolvi C, Tumini E, Plevani P, Muzi-Falconi M, Rotondo G. 107.  2013. Non-canonical CRL4A/4BCDT2 interacts with RAD18 to modulate post replication repair and cell survival. PLOS ONE 8:e60000 [Google Scholar]
  108. Shchebet A, Karpiuk O, Kremmer E, Eick D, Johnsen SA. 108.  2012. Phosphorylation by cyclin-dependent kinase-9 controls ubiquitin-conjugating enzyme-2A function. Cell Cycle 11:2122–27 [Google Scholar]
  109. Shen X, Mizuguchi G, Hamiche A, Wu C. 109.  2000. A chromatin remodelling complex involved in transcription and DNA processing. Nature 406:541–44 [Google Scholar]
  110. Shimada K, Oma Y, Schleker T, Kugou K, Ohta K. 110.  et al. 2008. Ino80 chromatin remodeling complex promotes recovery of stalled replication forks. Curr. Biol. 18:566–75 [Google Scholar]
  111. Simon AC, Zhou JC, Perera RL, van Deursen F, Evrin C. 111.  et al. 2014. A Ctf4 trimer couples the CMG helicase to DNA polymerase α in the eukaryotic replisome. Nature 510:293–97 [Google Scholar]
  112. Soria G, Gottifredi V. 112.  2010. PCNA-coupled p21 degradation after DNA damage: the exception that confirms the rule?. DNA Repair 9:358–64 [Google Scholar]
  113. Soria G, Podhajcer O, Prives C, Gottifredi V. 113.  2006. P21Cip1/WAF1 downregulation is required for efficient PCNA ubiquitination after UV irradiation. Oncogene 25:2829–38 [Google Scholar]
  114. Soria G, Speroni J, Podhajcer OL, Prives C, Gottifredi V. 114.  2008. p21 differentially regulates DNA replication and DNA-repair-associated processes after UV irradiation. J. Cell Sci. 121:3271–82 [Google Scholar]
  115. Soultanas P. 115.  2012. Loading mechanisms of ring helicases at replication origins. Mol. Microbiol. 84:6–16 [Google Scholar]
  116. Suzuki N, Ohashi E, Kolbanovskiy A, Geacintov NE, Grollman AP. 116.  et al. 2002. Translesion synthesis by human DNA polymerase κ on a DNA template containing a single stereoisomer of dG-(+)- or dG-(−)-anti-N2-BPDE (7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene). Biochemistry 41:6100–06 [Google Scholar]
  117. Tateishi S, Sakuraba Y, Masuyama S, Inoue H, Yamaizumi M. 117.  2000. Dysfunction of human Rad18 results in defective postreplication repair and hypersensitivity to multiple mutagens. PNAS 97:7927–32 [Google Scholar]
  118. Terai K, Abbas T, Jazaeri AA, Dutta A. 118.  2010. CRL4Cdt2 E3 ubiquitin ligase monoubiquitinates PCNA to promote translesion DNA synthesis. Mol. Cell 37:143–49 [Google Scholar]
  119. Tian F, Sharma S, Zou J, Lin S-Y, Wang B. 119.  et al. 2013. BRCA1 promotes the ubiquitination of PCNA and recruitment of translesion polymerases in response to replication blockade. PNAS 110:13558–63 [Google Scholar]
  120. Tsanov N, Kermi C, Coulombe P, Van der Laan S, Hodroj D, Maiorano D. 120.  2014. PIP degron proteins, substrates of CRL4Cdt2, and not PIP boxes, interfere with DNA polymerase η and κ focus formation on UV damage. Nucleic Acids Res. 42:3692–706 [Google Scholar]
  121. Tsuji Y, Watanabe K, Araki K, Shinohara M, Yamagata Y. 121.  et al. 2008. Recognition of forked and single-stranded DNA structures by human RAD18 complexed with RAD6B protein triggers its recruitment to stalled replication forks. Genes Cells 13:343–54 [Google Scholar]
  122. Ulrich HD. 122.  2011. Timing and spacing of ubiquitin-dependent DNA damage bypass. FEBS Lett. 585:2861–67 [Google Scholar]
  123. Ulrich HD, Jentsch S. 123.  2000. Two RING finger proteins mediate cooperation between ubiquitin-conjugating enzymes in DNA repair. EMBO J. 19:3388–97 [Google Scholar]
  124. Varanasi L, Do PM, Goluszko E, Martinez LA. 124.  2012. Rad18 is a transcriptional target of E2F3. Cell Cycle 11:1131–41 [Google Scholar]
  125. Varga A, Marcus AP, Himoto M, Iwai S, Szüts D. 125.  Analysis of CPD ultraviolet lesion bypass in chicken DT40 cells: polymerase η and PCNA ubiquitylation play identical roles. PLOS ONE 7:e52472 [Google Scholar]
  126. Veaute X, Jeusset J, Soustelle C, Kowalczykowski SC, Le Cam E, Fabre F. 126.  2003. The Srs2 helicase prevents recombination by disrupting Rad51 nucleoprotein filaments. Nature 423:309–12 [Google Scholar]
  127. Villamil MA, Chen J, Liang Q, Zhuang Z. 127.  2012. A noncanonical cysteine protease USP1 is activated through active site modulation by USP1-associated factor 1. Biochemistry 51:2829–39 [Google Scholar]
  128. Washington MT, Carlson KD, Freudenthal BD, Pryor JM. 128.  2010. Variations on a theme: eukaryotic Y-family DNA polymerases. Biochim. Biophys. Acta 1804:1113–23 [Google Scholar]
  129. Watanabe K, Tateishi S, Kawasuji M, Tsurimoto T, Inoue H, Yamaizumi M. 129.  2004. Rad18 guides polη to replication stalling sites through physical interaction and PCNA monoubiquitination. EMBO J. 23:3886–96 [Google Scholar]
  130. Windecker H, Ulrich HD. 130.  2008. Architecture and assembly of poly-SUMO chains on PCNA in Saccharomyces cerevisiae. J. Mol. Biol. 376:221–31 [Google Scholar]
  131. Wold MS. 131.  1997. Replication protein A: a heterotrimeric, single-stranded DNA-binding protein required for eukaryotic DNA metabolism. Annu. Rev. Biochem. 66:61–92 [Google Scholar]
  132. Wood A, Schneider J, Dover J, Johnston M, Shilatifard A. 132.  2005. The Bur1/Bur2 complex is required for histone H2B monoubiquitination by Rad6/Bre1 and histone methylation by COMPASS. Mol. Cell 20:589–99 [Google Scholar]
  133. Yanagihara H, Kobayashi J, Tateishi S, Kato A, Matsuura S. 133.  et al. 2011. NBS1 recruits RAD18 via a RAD6-like domain and regulates Pol η-dependent translesion DNA synthesis. Mol. Cell 43:788–97 [Google Scholar]
  134. Yang K, Weinacht CP, Zhuang Z. 134.  2013. Regulatory role of ubiquitin in eukaryotic DNA translesion synthesis. Biochemistry 52:3217–28 [Google Scholar]
  135. Yang XH, Shiotani B, Classon M, Zou L. 135.  2008. Chk1 and Claspin potentiate PCNA ubiquitination. Genes Dev. 22:1147–52 [Google Scholar]
  136. Yoon J-H, Prakash L, Prakash S. 136.  2009. Highly error-free role of DNA polymerase η in the replicative bypass of UV-induced pyrimidine dimers in mouse and human cells. PNAS 106:18219–24 [Google Scholar]
  137. Yoon J-H, Prakash L, Prakash S. 137.  2010. Error-free replicative bypass of (6-4) photoproducts by DNA polymerase ζ in mouse and human cells. Genes Dev. 24:123–28 [Google Scholar]
  138. Yu P, Huang B, Shen M, Lau C, Chan E. 138.  et al. 2001. p15PAF, a novel PCNA associated factor with increased expression in tumor tissues. Oncogene 20:484–89 [Google Scholar]
  139. Yuasa MS, Masutani C, Hirano A, Cohn MA, Yamaizumi M. 139.  et al. 2006. A human DNA polymerase η complex containing Rad18, Rad6 and Rev1; proteomic analysis and targeting of the complex to the chromatin-bound fraction of cells undergoing replication fork arrest. Genes Cells 11:731–44 [Google Scholar]
  140. Zhang S, Chea J, Meng X, Zhou Y, Lee EY, Lee MY. 140.  2008. PCNA is ubiquitinated by RNF8. Cell Cycle 7:3399–404 [Google Scholar]
  141. Zhang Y, Wu X, Guo D, Rechkoblit O, Wang Z. 141.  2002. Activities of human DNA polymerase κ in response to the major benzo[a]pyrene DNA adduct: error-free lesion bypass and extension synthesis from opposite the lesion. DNA Repair 1:559–69 [Google Scholar]
  142. Zheng L, Shen B. 142.  2011. Okazaki fragment maturation: nucleases take centre stage. J. Mol. Cell Biol. 3:23–30 [Google Scholar]
  143. Zhou B, Arnett DR, Yu X, Brewster A, Sowd GA. 143.  et al. 2012. Structural basis for the interaction of a hexameric replicative helicase with the regulatory subunit of human DNA polymerase α-primase. J. Biol. Chem. 287:26854–66 [Google Scholar]
  144. Ziv O, Geacintov N, Nakajima S, Yasui A, Livneh Z. 144.  2009. DNA polymerase ζ cooperates with polymerases κ and ι in translesion DNA synthesis across pyrimidine photodimers in cells from XPV patients. PNAS 106:11552–57 [Google Scholar]
/content/journals/10.1146/annurev-biophys-060414-033841
Loading
/content/journals/10.1146/annurev-biophys-060414-033841
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error