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Ubiquitination of PCNA and Its Essential Role in Eukaryotic Translesion Synthesis

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Abstract

Ubiquitin and ubiquitin-like proteins (Ubls) are now at the center stage of molecular and cell biology because of their diverse functions in many fundamentally important cellular processes. Besides the celebrated role of ubiquitin in the 26S proteasome-mediated protein degradation pathway, the non-proteolytic functions of ubiquitin are being uncovered at a fast pace. The prominent examples include membrane trafficking, innate immunity, kinase signaling, chromatin dynamics and DNA damage response. Researchers in the area of DNA damage response have witnessed rapid progress within the past decade, largely stimulated by the seminal findings that ubiquitination and SUMOylation of a key DNA replication/repair protein, proliferating cell nuclear antigen (PCNA), controls precisely how eukaryotic cells respond to different types of DNA damage, and how cellular DNA damage repair or tolerance pathways are selected to cope with damage in the DNA genome. Here, we will review the recent findings on translesion synthesis (TLS) and its regulation by PCNA ubiquitination in eukaryotes. We will discuss two prevalent models, i.e., the postreplicative gap-filling and the polymerase switch, which have been invoked to account for eukaryotic cells’ ability to overcome DNA damage associated replication blockade through TLS. Results from both in vitro reconstitution and from genetic systems will be discussed. We will also summarize the recent findings revealing the crosstalk between two major human DNA damage response pathways (the TLS and the Fanconi anemia pathways), and the ATR and ATM-independent regulation of PCNA ubiquitination. Lastly, new methods of preparing ubiquitinated PCNA will be reviewed. The availability of milligram levels of ubiquitinated PCNA will help our understanding of the molecular details in eukaryotic TLS.

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References

  1. Hershko, A., & Ciechanover, A. (1998). The ubiquitin system. Annual Review of Biochemistry, 67, 425–479.

    Article  PubMed  CAS  Google Scholar 

  2. Kirkin, V., & Dikic, I. (2007). Role of ubiquitin- and Ubl-binding proteins in cell signaling. Current Opinion in Cell Biology, 19, 199–205.

    Article  PubMed  CAS  Google Scholar 

  3. Kerscher, O., Felberbaum, R., & Hochstrasser, M. (2006). Modification of proteins by ubiquitin and ubiquitin-like proteins. Annu Rev Cell Dev Biol, 22, 159–180.

    Article  PubMed  CAS  Google Scholar 

  4. Welchman, R. L., Gordon, C., & Mayer, R. J. (2005). Ubiquitin and ubiquitin-like proteins as multifunctional signals. Nat Rev Mol Cell Biol, 6, 599–609.

    Article  PubMed  CAS  Google Scholar 

  5. Peng, J., Schwartz, D., Elias, J. E., Thoreen, C. C., Cheng, D., Marsischky, G., et al. (2003). A proteomics approach to understanding protein ubiquitination. Nature Biotechnology, 21, 921–926.

    Article  PubMed  CAS  Google Scholar 

  6. Nijman, S. M., Luna-Vargas, M. P., Velds, A., Brummelkamp, T. R., Dirac, A. M., Sixma, T. K., et al. (2005). A genomic and functional inventory of deubiquitinating enzymes. Cell, 123, 773–786.

    Article  PubMed  CAS  Google Scholar 

  7. Kannouche, P. L., Wing, J., & Lehmann, A. R. (2004). Interaction of human DNA polymerase eta with monoubiquitinated PCNA: a possible mechanism for the polymerase switch in response to DNA damage. Molecular Cell, 14, 491–500.

    Article  PubMed  CAS  Google Scholar 

  8. Watanabe, K., Tateishi, S., Kawasuji, M., Tsurimoto, T., Inoue, H., & Yamaizumi, M. (2004). Rad18 guides poleta to replication stalling sites through physical interaction and PCNA monoubiquitination. EMBO Journal, 23, 3886–3896.

    Article  PubMed  CAS  Google Scholar 

  9. Bienko, M., Green, C. M., Crosetto, N., Rudolf, F., Zapart, G., Coull, B., et al. (2005). Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis. Science, 310, 1821–1824.

    Article  PubMed  CAS  Google Scholar 

  10. Wood, A., Garg, P., & Burgers, P. M. (2007). A ubiquitin-binding motif in the translesion DNA polymerase Rev1 mediates its essential functional interaction with ubiquitinated proliferating cell nuclear antigen in response to DNA damage. Journal of Biological Chemistry, 282, 20256–20263.

    Article  PubMed  CAS  Google Scholar 

  11. Parker, J. L., Bielen, A. B., Dikic, I., & Ulrich, H. D. (2007). Contributions of ubiquitin- and PCNA-binding domains to the activity of Polymerase eta in Saccharomyces cerevisiae. Nucleic Acids Research, 35, 881–889.

    Article  PubMed  CAS  Google Scholar 

  12. Broomfield, S., Chow, B. L., & Xiao, W. (1998). MMS2, encoding a ubiquitin-conjugating-enzyme-like protein, is a member of the yeast error-free postreplication repair pathway. Proceedings of the National Academy of Sciences of the United States of America, 95, 5678–5683.

    Article  PubMed  CAS  Google Scholar 

  13. Brusky, J., Zhu, Y., & Xiao, W. (2000). UBC13, a DNA-damage-inducible gene, is a member of the error-free postreplication repair pathway in Saccharomyces cerevisiae. Current Genetics, 37, 168–174.

    Article  PubMed  CAS  Google Scholar 

  14. Branzei, D., Seki, M., & Enomoto, T. (2004). Rad18/Rad5/Mms2-mediated polyubiquitination of PCNA is implicated in replication completion during replication stress. Genes Cells, 9, 1031–1042.

    Article  PubMed  CAS  Google Scholar 

  15. Unk, I., Hajdu, I., Fatyol, K., Szakal, B., Blastyak, A., Bermudez, V., et al. (2006). Human SHPRH is a ubiquitin ligase for Mms2-Ubc13-dependent polyubiquitination of proliferating cell nuclear antigen. Proceedings of the National Academy of Sciences of the United States of America, 103, 18107–18112.

    Article  PubMed  CAS  Google Scholar 

  16. Chiu, R. K., Brun, J., Ramaekers, C., Theys, J., Weng, L., Lambin, P., et al. (2006). Lysine 63-polyubiquitination guards against translesion synthesis-induced mutations. PLoS Genet, 2, e116.

    Article  PubMed  Google Scholar 

  17. Motegi, A., Sood, R., Moinova, H., Markowitz, S. D., Liu, P. P., & Myung, K. (2006). Human SHPRH suppresses genomic instability through proliferating cell nuclear antigen polyubiquitination. Journal of Cell Biology, 175, 703–708.

    Article  PubMed  CAS  Google Scholar 

  18. Motegi, A., Liaw, H. J., Lee, K. Y., Roest, H. P., Maas, A., Wu, X., et al. (2008). Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks. Proceedings of the National Academy of Sciences of the United States of America, 105, 12411–12416.

    Article  PubMed  CAS  Google Scholar 

  19. Unk, I., Hajdu, I., Fatyol, K., Hurwitz, J., Yoon, J. H., Prakash, L., et al. (2008). Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination. Proceedings of the National Academy of Sciences of the United States of America, 105, 3768–3773.

    Article  PubMed  CAS  Google Scholar 

  20. Hoege, C., Pfander, B., Moldovan, G. L., Pyrowolakis, G., & Jentsch, S. (2002). RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO. Nature, 419, 135–141.

    Article  PubMed  CAS  Google Scholar 

  21. Papouli, E., Chen, S., Davies, A. A., Huttner, D., Krejci, L., Sung, P., et al. (2005). Crosstalk between SUMO and ubiquitin on PCNA is mediated by recruitment of the helicase Srs2p. Molecular Cell, 19, 123–133.

    Article  PubMed  CAS  Google Scholar 

  22. Pfander, B., Moldovan, G. L., Sacher, M., Hoege, C., & Jentsch, S. (2005). SUMO-modified PCNA recruits Srs2 to prevent recombination during S phase. Nature, 436, 428–433.

    PubMed  CAS  Google Scholar 

  23. Moldovan, G. L., Pfander, B., & Jentsch, S. (2006). PCNA controls establishment of sister chromatid cohesion during S phase. Molecular Cell, 23, 723–732.

    Article  PubMed  CAS  Google Scholar 

  24. Stelter, P., & Ulrich, H. D. (2003). Control of spontaneous and damage-induced mutagenesis by SUMO and ubiquitin conjugation. Nature, 425, 188–191.

    Article  PubMed  CAS  Google Scholar 

  25. Zhang, S., Chea, J., Meng, X., Zhou, Y., Lee, E. Y., & Lee, M. Y. (2008). PCNA is ubiquitinated by RNF8. Cell Cycle, 7, 3399–3404.

    Article  PubMed  CAS  Google Scholar 

  26. Terai, K., Abbas, T., Jazaeri, A. A., & Dutta, A. (2010). CRL4(Cdt2) E3 ubiquitin ligase monoubiquitinates PCNA to promote translesion DNA synthesis. Molecular Cell, 37, 143–149.

    Article  PubMed  CAS  Google Scholar 

  27. Das-Bradoo, S., Nguyen, H. D., Wood, J. L., Ricke, R. M., Haworth, J. C., & Bielinsky, A. K. (2010). Defects in DNA ligase I trigger PCNA ubiquitination at Lys 107. Nature Cell Biology, 12, 74–79. (Supp pp 71–20).

    Article  PubMed  CAS  Google Scholar 

  28. Yao, N. Y., & O’Donnell, M. (2009). Replisome structure and conformational dynamics underlie fork progression past obstacles. Current Opinion in Cell Biology, 21, 336–343.

    Article  PubMed  CAS  Google Scholar 

  29. Kunkel, T. A., & Burgers, P. M. (2008). Dividing the workload at a eukaryotic replication fork. Trends in Cell Biology, 18, 521–527.

    Article  PubMed  CAS  Google Scholar 

  30. Benkovic, S. J., Valentine, A. M., & Salinas, F. (2001). Replisome-mediated DNA replication. Annual Review of Biochemistry, 70, 181–208.

    Article  PubMed  CAS  Google Scholar 

  31. Ohmori, H., Friedberg, E. C., Fuchs, R. P., Goodman, M. F., Hanaoka, F., Hinkle, D., et al. (2001). The Y-family of DNA polymerases. Molecular Cell, 8, 7–8.

    Article  PubMed  CAS  Google Scholar 

  32. Higgins, N. P., Kato, K., & Strauss, B. (1976). A model for replication repair in mammalian cells. Journal of Molecular Biology, 101, 417–425.

    Article  PubMed  CAS  Google Scholar 

  33. Atkinson, J., & McGlynn, P. (2009). Replication fork reversal and the maintenance of genome stability. Nucleic Acids Research, 37, 3475–3492.

    Article  PubMed  CAS  Google Scholar 

  34. Prakash, S., Johnson, R. E., & Prakash, L. (2005). Eukaryotic translesion synthesis DNA polymerases: Specificity of structure and function. Annual Review of Biochemistry, 74, 317–353.

    Article  PubMed  CAS  Google Scholar 

  35. Washington, M. T., Carlson, K. D., Freudenthal, B. D., & Pryor, J. M. (2010). Variations on a theme: eukaryotic Y-family DNA polymerases. Biochimica et Biophysica Acta, 1804, 1113–1123.

    PubMed  CAS  Google Scholar 

  36. Rupp, W. D., & Howard-Flanders, P. (1968). Discontinuities in the DNA synthesized in an excision-defective strain of Escherichia coli following ultraviolet irradiation. Journal of Molecular Biology, 31, 291–304.

    Article  PubMed  CAS  Google Scholar 

  37. Lehmann, A. R. (1972). Postreplication repair of DNA in ultraviolet-irradiated mammalian cells. Journal of Molecular Biology, 66, 319–337.

    Article  PubMed  CAS  Google Scholar 

  38. Prakash, L. (1981). Characterization of postreplication repair in Saccharomyces cerevisiae and effects of rad6, rad18, rev3 and rad52 mutations. Molecular and General Genetics, 184, 471–478.

    Article  PubMed  CAS  Google Scholar 

  39. Bridges, B. A., & Sedgwick, S. G. (1974). Effect of photoreactivation on the filling of gaps in deoxyribonucleic acid synthesized after exposure of Escherichia coli to ultraviolet light. Journal of Bacteriology, 117, 1077–1081.

    PubMed  CAS  Google Scholar 

  40. Howard-Flanders, P., Rupp, W. D., Wilkins, B. M., & Cole, R. S. (1968). DNA replication and recombination after UV irradiation. Cold Spring Harbor Symposia on Quantitative Biology, 33, 195–207.

    PubMed  CAS  Google Scholar 

  41. Lemontt, J. F. (1971). Mutants of yeast defective in mutation induced by ultraviolet light. Genetics, 68, 21–33.

    PubMed  CAS  Google Scholar 

  42. Lawrence, C. W., & Christensen, R. (1976). UV mutagenesis in radiation-sensitive strains of yeast. Genetics, 82, 207–232.

    PubMed  CAS  Google Scholar 

  43. Bailly, V., Lamb, J., Sung, P., Prakash, S., & Prakash, L. (1994). Specific complex formation between yeast RAD6 and RAD18 proteins: a potential mechanism for targeting RAD6 ubiquitin-conjugating activity to DNA damage sites. Genes and Development, 8, 811–820.

    Article  PubMed  CAS  Google Scholar 

  44. Friedberg, E. C., Lehmann, A. R., & Fuchs, R. P. (2005). Trading places: how do DNA polymerases switch during translesion DNA synthesis? Molecular Cell, 18, 499–505.

    Article  PubMed  CAS  Google Scholar 

  45. Zhuang, Z., & Ai, Y. (2010). Processivity factor of DNA polymerase and its expanding role in normal and translesion DNA synthesis. Biochimica et Biophysica Acta, 1804, 1081–1093.

    PubMed  CAS  Google Scholar 

  46. Sutton, M. D. (2009). Coordinating DNA polymerase traffic during high and low fidelity synthesis. Biochim Biophys Acta, 1804(5), 1167–1179.

    PubMed  Google Scholar 

  47. Pages, V., & Fuchs, R. P. (2002). How DNA lesions are turned into mutations within cells? Oncogene, 21, 8957–8966.

    Article  PubMed  CAS  Google Scholar 

  48. Indiani, C., McInerney, P., Georgescu, R., Goodman, M. F., & O’Donnell, M. (2005). A sliding-clamp toolbelt binds high- and low-fidelity DNA polymerases simultaneously. Mol Cell, 19, 805–815.

    Article  PubMed  CAS  Google Scholar 

  49. Fujii, S., & Fuchs, R. P. (2004). Defining the position of the switches between replicative and bypass DNA polymerases. EMBO Journal, 23, 4342–4352.

    Article  PubMed  CAS  Google Scholar 

  50. Heltzel, J. M., Maul, R. W., Scouten Ponticelli, S. K., & Sutton, M. D. (2009). A model for DNA polymerase switching involving a single cleft and the rim of the sliding clamp. Proceedings of the National Academy of Sciences of the United States of America, 106, 12664–12669.

    Article  PubMed  CAS  Google Scholar 

  51. Furukohri, A., Goodman, M. F., & Maki, H. (2008). A dynamic polymerase exchange with Escherichia coli DNA polymerase IV replacing DNA polymerase III on the sliding clamp. Journal of Biological Chemistry, 283, 11260–11269.

    Article  PubMed  CAS  Google Scholar 

  52. Indiani, C., Langston, L. D., Yurieva, O., Goodman, M. F., & O’Donnell, M. (2009). Translesion DNA polymerases remodel the replisome and alter the speed of the replicative helicase. Proceedings of the National Academy of Sciences of the United States of America, 106, 6031–6038.

    Article  PubMed  CAS  Google Scholar 

  53. Pages, V., & Fuchs, R. P. (2003). Uncoupling of leading- and lagging-strand DNA replication during lesion bypass in vivo. Science, 300, 1300–1303.

    Article  PubMed  CAS  Google Scholar 

  54. Kuban, W., Banach-Orlowska, M., Bialoskorska, M., Lipowska, A., Schaaper, R. M., Jonczyk, P., et al. (2005). Mutator phenotype resulting from DNA polymerase IV overproduction in Escherichia coli: preferential mutagenesis on the lagging strand. Journal of Bacteriology, 187, 6862–6866.

    Article  PubMed  CAS  Google Scholar 

  55. Uchida, K., Furukohri, A., Shinozaki, Y., Mori, T., Ogawara, D., Kanaya, S., et al. (2008). Overproduction of Escherichia coli DNA polymerase DinB (Pol IV) inhibits replication fork progression and is lethal. Molecular Microbiology, 70, 608–622.

    Article  PubMed  CAS  Google Scholar 

  56. Zhuang, Z., Johnson, R. E., Haracska, L., Prakash, L., Prakash, S., & Benkovic, S. J. (2008). Regulation of polymerase exchange between Poleta and Poldelta by monoubiquitination of PCNA and the movement of DNA polymerase holoenzyme. Proceedings of the National Academy of Sciences of the United States of America, 105, 5361–5366.

    Article  PubMed  CAS  Google Scholar 

  57. Masuda, Y., Piao, J., & Kamiya, K. (2010). DNA replication-coupled PCNA mono-ubiquitination and polymerase switching in a human in vitro system. Journal of Molecular Biology, 396, 487–500.

    Article  PubMed  CAS  Google Scholar 

  58. Schmutz, V., Wagner, J., Janel-Bintz, R., Fuchs, R. P., & Cordonnier, A. M. (2007). Requirements for PCNA monoubiquitination in human cell-free extracts. DNA Repair (Amsterdam), 6, 1726–1731.

    Article  CAS  Google Scholar 

  59. Leach, C. A., & Michael, W. M. (2005). Ubiquitin/SUMO modification of PCNA promotes replication fork progression in Xenopus laevis egg extracts. Journal of Cell Biology, 171, 947–954.

    Article  PubMed  CAS  Google Scholar 

  60. Tissier, A., Janel-Bintz, R., Coulon, S., Klaile, E., Kannouche, P., Fuchs, R. P., et al. (2010). Crosstalk between replicative and translesional DNA polymerases: PDIP38 interacts directly with Poleta. DNA Repair (Amsterdam), 9, 922–928.

    Article  CAS  Google Scholar 

  61. Svoboda, D. L., & Vos, J. M. (1995). Differential replication of a single, UV-induced lesion in the leading or lagging strand by a human cell extract: fork uncoupling or gap formation. Proceedings of the National Academy of Sciences of the United States of America, 92, 11975–11979.

    Article  PubMed  CAS  Google Scholar 

  62. Cordeiro-Stone, M., Makhov, A. M., Zaritskaya, L. S., & Griffith, J. D. (1999). Analysis of DNA replication forks encountering a pyrimidine dimer in the template to the leading strand. Journal of Molecular Biology, 289, 1207–1218.

    Article  PubMed  CAS  Google Scholar 

  63. Lopes, M., Foiani, M., & Sogo, J. M. (2006). Multiple mechanisms control chromosome integrity after replication fork uncoupling and restart at irreparable UV lesions. Molecular Cell, 21, 15–27.

    Article  PubMed  CAS  Google Scholar 

  64. Daigaku, Y., Davies, A. A., & Ulrich, H. D. (2010). Ubiquitin-dependent DNA damage bypass is separable from genome replication. Nature, 465, 951–955.

    Article  PubMed  CAS  Google Scholar 

  65. Karras, G. I., & Jentsch, S. (2010). The RAD6 DNA damage tolerance pathway operates uncoupled from the replication fork and is functional beyond S phase. Cell, 141, 255–267.

    Article  PubMed  CAS  Google Scholar 

  66. Alpi, A. F., & Patel, K. J. (2009). Monoubiquitination in the Fanconi anemia DNA damage response pathway. DNA Repair (Amsterdam), 8, 430–435.

    Article  CAS  Google Scholar 

  67. Kook, H. (2005). Fanconi anemia: Current management. Hematology, 10(Suppl 1), 108–110.

    Article  PubMed  CAS  Google Scholar 

  68. Garcia-Higuera, I., Taniguchi, T., Ganesan, S., Meyn, M. S., Timmers, C., Hejna, J., et al. (2001). Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway. Molecular Cell, 7, 249–262.

    Article  PubMed  CAS  Google Scholar 

  69. Montes de Oca, R., Andreassen, P. R., Margossian, S. P., Gregory, R. C., Taniguchi, T., Wang, X., et al. (2005). Regulated interaction of the Fanconi anemia protein, FANCD2, with chromatin. Blood, 105, 1003–1009.

    Article  PubMed  Google Scholar 

  70. Taniguchi, T., Garcia-Higuera, I., Andreassen, P. R., Gregory, R. C., Grompe, M., & D’Andrea, A. D. (2002). S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with BRCA1 and RAD51. Blood, 100, 2414–2420.

    Article  PubMed  CAS  Google Scholar 

  71. Wang, X., Andreassen, P. R., & D’Andrea, A. D. (2004). Functional interaction of monoubiquitinated FANCD2 and BRCA2/FANCD1 in chromatin. Molecular and Cellular Biology, 24, 5850–5862.

    Article  PubMed  CAS  Google Scholar 

  72. Hussain, S., Wilson, J. B., Medhurst, A. L., Hejna, J., Witt, E., Ananth, S., et al. (2004). Direct interaction of FANCD2 with BRCA2 in DNA damage response pathways. Human Molecular Genetics, 13, 1241–1248.

    Article  PubMed  CAS  Google Scholar 

  73. Niedzwiedz, W., Mosedale, G., Johnson, M., Ong, C. Y., Pace, P., & Patel, K. J. (2004). The Fanconi anaemia gene FANCC promotes homologous recombination and error-prone DNA repair. Molecular Cell, 15, 607–620.

    Article  PubMed  CAS  Google Scholar 

  74. Ishiai, M., Kitao, H., Smogorzewska, A., Tomida, J., Kinomura, A., Uchida, E., et al. (2008). FANCI phosphorylation functions as a molecular switch to turn on the Fanconi anemia pathway. Nature Structural & Molecular Biology, 15, 1138–1146.

    Article  CAS  Google Scholar 

  75. Geng, L., Huntoon, C. J., & Karnitz, L. M. (2010). RAD18-mediated ubiquitination of PCNA activates the Fanconi anemia DNA repair network. Journal of Cell Biology, 191, 249–257.

    Article  PubMed  CAS  Google Scholar 

  76. Nijman, S. M., Huang, T. T., Dirac, A. M., Brummelkamp, T. R., Kerkhoven, R. M., D’Andrea, A. D., et al. (2005). The deubiquitinating enzyme USP1 regulates the Fanconi anemia pathway. Molecular Cell, 17, 331–339.

    Article  PubMed  CAS  Google Scholar 

  77. Chang, D. J., Lupardus, P. J., & Cimprich, K. A. (2006). Monoubiquitination of proliferating cell nuclear antigen induced by stalled replication requires uncoupling of DNA polymerase and mini-chromosome maintenance helicase activities. Journal of Biological Chemistry, 281, 32081–32088.

    Article  PubMed  CAS  Google Scholar 

  78. Davies, A. A., Huttner, D., Daigaku, Y., Chen, S., & Ulrich, H. D. (2008). Activation of ubiquitin-dependent DNA damage bypass is mediated by replication protein a. Molecular Cell, 29, 625–636.

    Article  PubMed  CAS  Google Scholar 

  79. Zou, L. (2007). Single- and double-stranded DNA: building a trigger of ATR-mediated DNA damage response. Genes and Development, 21, 879–885.

    Article  PubMed  CAS  Google Scholar 

  80. Smits, V. A., Warmerdam, D. O., Martin, Y., & Freire, R. (2010). Mechanisms of ATR-mediated checkpoint signalling. Frontier Bioscience, 15, 840–853.

    Article  CAS  Google Scholar 

  81. Derheimer, F. A., & Kastan, M. B. (2010). Multiple roles of ATM in monitoring and maintaining DNA integrity. FEBS Letters, 584, 3675–3681.

    Article  PubMed  CAS  Google Scholar 

  82. Bi, X., Barkley, L. R., Slater, D. M., Tateishi, S., Yamaizumi, M., Ohmori, H., et al. (2006). Rad18 regulates DNA polymerase kappa and is required for recovery from S-phase checkpoint-mediated arrest. Molecular and Cellular Biology, 26, 3527–3540.

    Article  PubMed  CAS  Google Scholar 

  83. Niimi, A., Brown, S., Sabbioneda, S., Kannouche, P. L., Scott, A., Yasui, A., et al. (2008). Regulation of proliferating cell nuclear antigen ubiquitination in mammalian cells. Proceedings of the National Academy of Sciences of the United States of America, 105, 16125–16130.

    Article  PubMed  CAS  Google Scholar 

  84. Yang, X. H., Shiotani, B., Classon, M., & Zou, L. (2008). Chk1 and Claspin potentiate PCNA ubiquitination. Genes and Development, 22, 1147–1152.

    Article  PubMed  CAS  Google Scholar 

  85. Yang, X. H., & Zou, L. (2009). Dual functions of DNA replication forks in checkpoint signaling and PCNA ubiquitination. Cell Cycle, 8, 191–194.

    Article  PubMed  CAS  Google Scholar 

  86. Brun, J., Chiu, R. K., Wouters, B. G., & Gray, D. A. (2010). Regulation of PCNA polyubiquitination in human cells. BMC Research Notes, 3, 85.

    Article  PubMed  Google Scholar 

  87. Haracska, L., Unk, I., Prakash, L., & Prakash, S. (2006). Ubiquitination of yeast proliferating cell nuclear antigen and its implications for translesion DNA synthesis. Proceedings of the National Academy of Sciences of the United States of America, 103, 6477–6482.

    Article  PubMed  CAS  Google Scholar 

  88. Garg, P., & Burgers, P. M. (2005). Ubiquitinated proliferating cell nuclear antigen activates translesion DNA polymerases eta and REV1. Proceedings of the National Academy of Sciences of the United States of America, 102, 18361–18366.

    Article  PubMed  CAS  Google Scholar 

  89. Chen, S., Levin, M. K., Sakato, M., Zhou, Y., & Hingorani, M. M. (2009). Mechanism of ATP-driven PCNA clamp loading by S. cerevisiae RFC. Journal of Molecular Biology, 388, 431–442.

    Article  PubMed  CAS  Google Scholar 

  90. Gomes, X. V., & Burgers, P. M. (2001). ATP utilization by yeast replication factor C. I. ATP-mediated interaction with DNA and with proliferating cell nuclear antigen. Journal of Biological Chemistry, 276, 34768–34775.

    Article  PubMed  CAS  Google Scholar 

  91. Chen, J., Ai, Y., Wang, J., Haracska, L., & Zhuang, Z. (2010). Chemically ubiquitylated PCNA as a probe for eukaryotic translesion DNA synthesis. Nature Chemical Biology, 6, 270–272.

    Article  PubMed  CAS  Google Scholar 

  92. Chatterjee, C., McGinty, R. K., Fierz, B., & Muir, T. W. (2010). Disulfide-directed histone ubiquitination reveals plasticity in hDot1L activation. Nature Chemical Biology, 6, 267–269.

    Article  PubMed  CAS  Google Scholar 

  93. Freudenthal, B. D., Gakhar, L., Ramaswamy, S., & Washington, M. T. (2010). Structure of monoubiquitinated PCNA and implications for translesion synthesis and DNA polymerase exchange. Nature Structural & Molecular Biology, 17, 479–484.

    Article  CAS  Google Scholar 

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Acknowledgments

We thank Yongxing Ai for the assistance in making Fig. 4. This work was supported in part by a grant from the US National Science Foundation (MCB-0953764).

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Correspondence to Zhihao Zhuang.

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Junjun Chen and William Bozza contributed equally to this work.

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Chen, J., Bozza, W. & Zhuang, Z. Ubiquitination of PCNA and Its Essential Role in Eukaryotic Translesion Synthesis. Cell Biochem Biophys 60, 47–60 (2011). https://doi.org/10.1007/s12013-011-9187-3

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