Cell Biochemistry and Biophysics

, Volume 60, Issue 1–2, pp 47–60 | Cite as

Ubiquitination of PCNA and Its Essential Role in Eukaryotic Translesion Synthesis

Original Paper


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.


DNA damage DNA repair Ubiquitin 



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).


  1. 1.
    Hershko, A., & Ciechanover, A. (1998). The ubiquitin system. Annual Review of Biochemistry, 67, 425–479.PubMedCrossRefGoogle Scholar
  2. 2.
    Kirkin, V., & Dikic, I. (2007). Role of ubiquitin- and Ubl-binding proteins in cell signaling. Current Opinion in Cell Biology, 19, 199–205.PubMedCrossRefGoogle Scholar
  3. 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.PubMedCrossRefGoogle Scholar
  4. 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.PubMedCrossRefGoogle Scholar
  5. 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.PubMedCrossRefGoogle Scholar
  6. 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.PubMedCrossRefGoogle Scholar
  7. 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.PubMedCrossRefGoogle Scholar
  8. 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.PubMedCrossRefGoogle Scholar
  9. 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.PubMedCrossRefGoogle Scholar
  10. 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.PubMedCrossRefGoogle Scholar
  11. 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.PubMedCrossRefGoogle Scholar
  12. 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.PubMedCrossRefGoogle Scholar
  13. 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.PubMedCrossRefGoogle Scholar
  14. 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.PubMedCrossRefGoogle Scholar
  15. 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.PubMedCrossRefGoogle Scholar
  16. 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.PubMedCrossRefGoogle Scholar
  17. 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.PubMedCrossRefGoogle Scholar
  18. 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.PubMedCrossRefGoogle Scholar
  19. 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.PubMedCrossRefGoogle Scholar
  20. 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.PubMedCrossRefGoogle Scholar
  21. 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.PubMedCrossRefGoogle Scholar
  22. 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.PubMedGoogle Scholar
  23. 23.
    Moldovan, G. L., Pfander, B., & Jentsch, S. (2006). PCNA controls establishment of sister chromatid cohesion during S phase. Molecular Cell, 23, 723–732.PubMedCrossRefGoogle Scholar
  24. 24.
    Stelter, P., & Ulrich, H. D. (2003). Control of spontaneous and damage-induced mutagenesis by SUMO and ubiquitin conjugation. Nature, 425, 188–191.PubMedCrossRefGoogle Scholar
  25. 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.PubMedCrossRefGoogle Scholar
  26. 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.PubMedCrossRefGoogle Scholar
  27. 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).PubMedCrossRefGoogle Scholar
  28. 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.PubMedCrossRefGoogle Scholar
  29. 29.
    Kunkel, T. A., & Burgers, P. M. (2008). Dividing the workload at a eukaryotic replication fork. Trends in Cell Biology, 18, 521–527.PubMedCrossRefGoogle Scholar
  30. 30.
    Benkovic, S. J., Valentine, A. M., & Salinas, F. (2001). Replisome-mediated DNA replication. Annual Review of Biochemistry, 70, 181–208.PubMedCrossRefGoogle Scholar
  31. 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.PubMedCrossRefGoogle Scholar
  32. 32.
    Higgins, N. P., Kato, K., & Strauss, B. (1976). A model for replication repair in mammalian cells. Journal of Molecular Biology, 101, 417–425.PubMedCrossRefGoogle Scholar
  33. 33.
    Atkinson, J., & McGlynn, P. (2009). Replication fork reversal and the maintenance of genome stability. Nucleic Acids Research, 37, 3475–3492.PubMedCrossRefGoogle Scholar
  34. 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.PubMedCrossRefGoogle Scholar
  35. 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.PubMedGoogle Scholar
  36. 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.PubMedCrossRefGoogle Scholar
  37. 37.
    Lehmann, A. R. (1972). Postreplication repair of DNA in ultraviolet-irradiated mammalian cells. Journal of Molecular Biology, 66, 319–337.PubMedCrossRefGoogle Scholar
  38. 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.PubMedCrossRefGoogle Scholar
  39. 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.PubMedGoogle Scholar
  40. 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.PubMedGoogle Scholar
  41. 41.
    Lemontt, J. F. (1971). Mutants of yeast defective in mutation induced by ultraviolet light. Genetics, 68, 21–33.PubMedGoogle Scholar
  42. 42.
    Lawrence, C. W., & Christensen, R. (1976). UV mutagenesis in radiation-sensitive strains of yeast. Genetics, 82, 207–232.PubMedGoogle Scholar
  43. 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.PubMedCrossRefGoogle Scholar
  44. 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.PubMedCrossRefGoogle Scholar
  45. 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.PubMedGoogle Scholar
  46. 46.
    Sutton, M. D. (2009). Coordinating DNA polymerase traffic during high and low fidelity synthesis. Biochim Biophys Acta, 1804(5), 1167–1179.PubMedGoogle Scholar
  47. 47.
    Pages, V., & Fuchs, R. P. (2002). How DNA lesions are turned into mutations within cells? Oncogene, 21, 8957–8966.PubMedCrossRefGoogle Scholar
  48. 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.PubMedCrossRefGoogle Scholar
  49. 49.
    Fujii, S., & Fuchs, R. P. (2004). Defining the position of the switches between replicative and bypass DNA polymerases. EMBO Journal, 23, 4342–4352.PubMedCrossRefGoogle Scholar
  50. 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.PubMedCrossRefGoogle Scholar
  51. 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.PubMedCrossRefGoogle Scholar
  52. 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.PubMedCrossRefGoogle Scholar
  53. 53.
    Pages, V., & Fuchs, R. P. (2003). Uncoupling of leading- and lagging-strand DNA replication during lesion bypass in vivo. Science, 300, 1300–1303.PubMedCrossRefGoogle Scholar
  54. 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.PubMedCrossRefGoogle Scholar
  55. 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.PubMedCrossRefGoogle Scholar
  56. 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.PubMedCrossRefGoogle Scholar
  57. 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.PubMedCrossRefGoogle Scholar
  58. 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.CrossRefGoogle Scholar
  59. 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.PubMedCrossRefGoogle Scholar
  60. 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.CrossRefGoogle Scholar
  61. 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.PubMedCrossRefGoogle Scholar
  62. 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.PubMedCrossRefGoogle Scholar
  63. 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.PubMedCrossRefGoogle Scholar
  64. 64.
    Daigaku, Y., Davies, A. A., & Ulrich, H. D. (2010). Ubiquitin-dependent DNA damage bypass is separable from genome replication. Nature, 465, 951–955.PubMedCrossRefGoogle Scholar
  65. 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.PubMedCrossRefGoogle Scholar
  66. 66.
    Alpi, A. F., & Patel, K. J. (2009). Monoubiquitination in the Fanconi anemia DNA damage response pathway. DNA Repair (Amsterdam), 8, 430–435.CrossRefGoogle Scholar
  67. 67.
    Kook, H. (2005). Fanconi anemia: Current management. Hematology, 10(Suppl 1), 108–110.PubMedCrossRefGoogle Scholar
  68. 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.PubMedCrossRefGoogle Scholar
  69. 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.PubMedCrossRefGoogle Scholar
  70. 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.PubMedCrossRefGoogle Scholar
  71. 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.PubMedCrossRefGoogle Scholar
  72. 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.PubMedCrossRefGoogle Scholar
  73. 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.PubMedCrossRefGoogle Scholar
  74. 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.CrossRefGoogle Scholar
  75. 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.PubMedCrossRefGoogle Scholar
  76. 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.PubMedCrossRefGoogle Scholar
  77. 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.PubMedCrossRefGoogle Scholar
  78. 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.PubMedCrossRefGoogle Scholar
  79. 79.
    Zou, L. (2007). Single- and double-stranded DNA: building a trigger of ATR-mediated DNA damage response. Genes and Development, 21, 879–885.PubMedCrossRefGoogle Scholar
  80. 80.
    Smits, V. A., Warmerdam, D. O., Martin, Y., & Freire, R. (2010). Mechanisms of ATR-mediated checkpoint signalling. Frontier Bioscience, 15, 840–853.CrossRefGoogle Scholar
  81. 81.
    Derheimer, F. A., & Kastan, M. B. (2010). Multiple roles of ATM in monitoring and maintaining DNA integrity. FEBS Letters, 584, 3675–3681.PubMedCrossRefGoogle Scholar
  82. 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.PubMedCrossRefGoogle Scholar
  83. 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.PubMedCrossRefGoogle Scholar
  84. 84.
    Yang, X. H., Shiotani, B., Classon, M., & Zou, L. (2008). Chk1 and Claspin potentiate PCNA ubiquitination. Genes and Development, 22, 1147–1152.PubMedCrossRefGoogle Scholar
  85. 85.
    Yang, X. H., & Zou, L. (2009). Dual functions of DNA replication forks in checkpoint signaling and PCNA ubiquitination. Cell Cycle, 8, 191–194.PubMedCrossRefGoogle Scholar
  86. 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.PubMedCrossRefGoogle Scholar
  87. 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.PubMedCrossRefGoogle Scholar
  88. 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.PubMedCrossRefGoogle Scholar
  89. 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.PubMedCrossRefGoogle Scholar
  90. 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.PubMedCrossRefGoogle Scholar
  91. 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.PubMedCrossRefGoogle Scholar
  92. 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.PubMedCrossRefGoogle Scholar
  93. 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.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Chemistry and BiochemistryUniversity of DelawareNewarkUSA

Personalised recommendations