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Functions of Multiple Clamp and Clamp-Loader Complexes in Eukaryotic DNA Replication

  • Eiji Ohashi
  • Toshiki TsurimotoEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1042)

Abstract

Proliferating cell nuclear antigen (PCNA) and replication factor C (RFC) were identified in the late 1980s as essential factors for replication of simian virus 40 DNA in human cells, by reconstitution of the reaction in vitro. Initially, they were only thought to be involved in the elongation stage of DNA replication. Subsequent studies have demonstrated that PCNA functions as more than a replication factor, through its involvement in multiple protein-protein interactions. PCNA appears as a functional hub on replicating and replicated chromosomal DNA and has an essential role in the maintenance genome integrity in proliferating cells.

Eukaryotes have multiple paralogues of sliding clamp, PCNA and its loader, RFC. The PCNA paralogues, RAD9, HUS1, and RAD1 form the heterotrimeric 9-1-1 ring that is similar to the PCNA homotrimeric ring, and the 9-1-1 clamp complex is loaded onto sites of DNA damage by its specific loader RAD17-RFC. This alternative clamp-loader system transmits DNA-damage signals in genomic DNA to the checkpoint-activation network and the DNA-repair apparatus.

Another two alternative loader complexes, CTF18-RFC and ELG1-RFC, have roles that are distinguishable from the role of the canonical loader, RFC. CTF18-RFC interacts with one of the replicative DNA polymerases, Polε, and loads PCNA onto leading-strand DNA, and ELG1-RFC unloads PCNA after ligation of lagging-strand DNA. In the progression of S phase, these alternative PCNA loaders maintain appropriate amounts of PCNA on the replicating sister DNAs to ensure that specific enzymes are tethered at specific chromosomal locations.

Keywords

DNA polymerase PCNA RFC PIP box Leading strand Lagging strand Chromatin Cohesion Unloading 

Notes

Acknowledgments

We would like to thank Dr. T. S. Takahashi (Kyushu University) for the comments on the manuscript. We apologize to those colleagues whose work is not cited because of space restrictions. This work is supported by Grants-in-aid for Scientific Research (KAKENHI) 25131714, 25440011, 26114714, and 16H04743.

References

  1. Abbas T, Sivaprasad U, Terai K, Amador V, Pagano M, Dutta A (2008) PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex. Genes Dev 22:2496–2506PubMedPubMedCentralCrossRefGoogle Scholar
  2. Abbas T, Shibata E, Park J, Jha S, Karnani N, Dutta A (2010) CRL4 Cdt2 regulates cell proliferation and histone gene expression by targeting PR-Set7/Set8 for degradation. Mol Cell 40:9–21PubMedPubMedCentralCrossRefGoogle Scholar
  3. Acevedo J, Yan S, Michael WM (2016) Direct binding to replication protein a (RPA)-coated single-stranded DNA allows recruitment of the ATR activator TopBP1 to sites of DNA damage. J Biol Chem 291:13124–13131PubMedPubMedCentralCrossRefGoogle Scholar
  4. Alabert C, Bukowski-Wills JC, Lee SB, Kustatscher G, Nakamura K, de Lima AF, Menard P, Mejlvang J, Rappsilber J, Groth A (2014) Nascent chromatin capture proteomics determines chromatin dynamics during DNA replication and identifies unknown fork components. Nat Cell Biol 16:281–293PubMedPubMedCentralCrossRefGoogle Scholar
  5. Arias EE, Walter JC (2005) Replication-dependent destruction of Cdt1 limits DNA replication to a single round per cell cycle in Xenopus egg extracts. Genes Dev 19:114–126PubMedPubMedCentralCrossRefGoogle Scholar
  6. Awasthi P, Foiani M, Kumar A (2015) ATM and ATR signaling at a glance. J Cell Sci 128:4255–4262PubMedCrossRefGoogle Scholar
  7. Aylon Y, Kupiec M (2003) The checkpoint protein Rad24 of saccharomyces cerevisiae is involved in processing double-strand break ends and in recombination partner choice. Mol Cell Biol 23(18):6585–6596Google Scholar
  8. Balakrishnan L, Brandt PD, Lindsey-Boltz LA, Sancar A, Bambara RA (2009) Long patch base excision repair proceeds via coordinated stimulation of the multienzyme DNA repair complex. J Biol Chem 284:15158–15172PubMedPubMedCentralCrossRefGoogle Scholar
  9. Bao S, Tibbetts RS, Brumbaugh KM, Fang Y, Richardson DA, Ali A, Chen SM, Abraham RT, Wang XF (2001) ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses. Nature 411:969–974PubMedCrossRefGoogle Scholar
  10. Bermudez VP, Lindsey-Boltz LA, Cesare AJ, Maniwa Y, Griffith JD, Hurwitz J, Sancar A (2003) Loading of the human 9-1-1 checkpoint complex onto DNA by the checkpoint clamp loader hRad17-replication factor C complex in vitro. Proc Natl Acad Sci U S A 100:1633–1638PubMedPubMedCentralCrossRefGoogle Scholar
  11. Bienko M, Green CM, Crosetto N, Rudolf F, Zapart G, Coull B, Kannouche P, Wider G, Peter M, Lehmann AR, Hofmann K, Dikic I (2005) Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis. Science 310:1821–1824PubMedCrossRefGoogle Scholar
  12. Boehm EM, Washington MT (2016) R.I.P. to the PIP: PCNA-binding motif no longer considered specific: PIP motifs and other related sequences are not distinct entities and can bind multiple proteins involved in genome maintenance. BioEssays 38:1117–1122PubMedPubMedCentralCrossRefGoogle Scholar
  13. Burgers PM (2009) Polymerase dynamics at the eukaryotic DNA replication fork. J Biol Chem 284:4041–4055PubMedPubMedCentralCrossRefGoogle Scholar
  14. Burtelow MA, Kaufmann SH, Karnitz LM (2000) Retention of the human Rad9 checkpoint complex in extraction-resistant nuclear complexes after DNA damage. J Biol Chem 275:26343–26348PubMedCrossRefGoogle Scholar
  15. Burtelow MA, Roos-Mattjus PM, Rauen M, Babendure JR, Karnitz LM (2001) Reconstitution and molecular analysis of the hRad9-hHus1-hRad1 (9-1-1) DNA damage responsive checkpoint complex. J Biol Chem 276:25903–25909PubMedCrossRefGoogle Scholar
  16. Bylund GO, Burgers PM (2005) Replication protein A-directed unloading of PCNA by the Ctf18 cohesion establishment complex. Mol Cell Biol 25:5445–5455PubMedPubMedCentralCrossRefGoogle Scholar
  17. Byun TS, Pacek M, Yee MC, Walter JC, Cimprich KA (2005) Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint. Genes Dev 19:1040–1052PubMedPubMedCentralCrossRefGoogle Scholar
  18. Carr AM, Lambert S (2013) Replication stress-induced genome instability: the dark side of replication maintenance by homologous recombination. J Mol Biol 425:4733–4744PubMedCrossRefGoogle Scholar
  19. Caspari T, Dahlen M, Kanter-Smoler G, Lindsay HD, Hofmann K, Papadimitriou K, Sunnerhagen P, Carr AM (2000) Characterization of Schizosaccharomyces pombe Hus1: a PCNA-related protein that associates with Rad1 and Rad9. Mol Cell Biol 74:1254–1262CrossRefGoogle Scholar
  20. Chen MJ, Lin YT, Lieberman HB, Chen G, Lee EY (2001) ATM-dependent phosphorylation of human Rad9 is required for ionizing radiation-induced checkpoint activation. J Biol Chem 276:16580–16586PubMedCrossRefGoogle Scholar
  21. Chen X, Paudyal SC, Chin RI, You Z (2013) PCNA promotes processive DNA end resection by Exo1. Nucleic Acids Res 41:9325–9338PubMedPubMedCentralCrossRefGoogle Scholar
  22. Choe KN, Moldovan GL (2017) Forging ahead through darkness: PCNA, still the principal conductor at the replication fork. Mol Cell 65:380–392PubMedCrossRefGoogle Scholar
  23. Chuang LC, Yew PR (2001) Regulation of nuclear transport and degradation of the Xenopus cyclin-dependent kinase inhibitor, p27Xic1. J Biol Chem 276:1610–1617PubMedCrossRefGoogle Scholar
  24. Chuang LS, Ian HI, Koh TW, Ng HH, Xu G, Li BF (1997) Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1. Science 277:1996–2000PubMedCrossRefGoogle Scholar
  25. Cimprich KA, Cortez D (2008) ATR: an essential regulator of genome integrity. Nat Rev Mol Cell Biol 9:616–627PubMedPubMedCentralCrossRefGoogle Scholar
  26. Cotta-Ramusino C, McDonald ER 3rd, Hurov K, Sowa ME, Harper JW, Elledge SJ (2011) A DNA damage response screen identifies RHINO, a 9-1-1 and TopBP1 interacting protein required for ATR signaling. Science 332:1313–1317PubMedPubMedCentralCrossRefGoogle Scholar
  27. Crabbé L, Thomas A, Pantesco V, De Vos J, Pasero P, Lengronne A (2010) Analysis of replication profiles reveals key role of RFC–Ctf18 in yeast replication stress response. Nat Struct Mol Biol 17:1391–1397PubMedCrossRefGoogle Scholar
  28. De March M, Merino N, Barrera-Vilarmau S, Crehuet R, Onesti S, Blanco FJ, De Biasio A (2017) Structural basis of human PCNA sliding on DNA. Nat Commun 8:13935PubMedPubMedCentralCrossRefGoogle Scholar
  29. Delacroix S, Wagner JM, Kobayashi M, Yamamoto K, Karnitz LM (2007) The Rad9-Hus1-Rad1 (9-1-1) clamp activates checkpoint signaling via TopBP1. Genes Dev 21:1472–1477PubMedPubMedCentralCrossRefGoogle Scholar
  30. Dianov GL, Sleeth KM, Dianova II, Allinson SL (2003) Repair of abasic sites in DNA. Mutat Res 531:157–163PubMedCrossRefGoogle Scholar
  31. Doré AS, Kilkenny ML, Rzechorzek NJ, Pearl LH (2009) Crystal structure of the rad9-rad1-hus1 DNA damage checkpoint complex--implications for clamp loading and regulation. Mol Cell 34:735–745PubMedCrossRefGoogle Scholar
  32. Dua R, Levy DL, Campbell JL (1999) Analysis of the essential functions of the C-terminal protein/protein interaction domain of Saccharomyces cerevisiae pol ε and its unexpected ability to support growth in the absence of the DNA polymerase domain. J Biol Chem 274:22283–22288PubMedCrossRefGoogle Scholar
  33. Duursma AM, Driscoll R, Elias JE, Cimprich KA (2013) A role for the MRN complex in ATR activation via TOPBP1 recruitment. Mol Cell 50:116–122PubMedPubMedCentralCrossRefGoogle Scholar
  34. Edmunds CE, Simpson LJ, Sale JE (2008) PCNA ubiquitination and REV1 define temporally distinct mechanisms for controlling translesion synthesis in the avian cell line DT40. Mol Cell 30:519–529PubMedCrossRefGoogle Scholar
  35. Ellison V, Stillman B (2003) Biochemical characterization of DNA damage checkpoint complexes: clamp loader and clamp complexes with specificity for 5′ recessed DNA. PLoS Biol 1:e33PubMedPubMedCentralCrossRefGoogle Scholar
  36. Fan J, Otterlei M, Wong HK, Tomkinson AE, Wilson DM 3rd (2004) XRCC1 co-localizes and physically interacts with PCNA. Nucleic Acids Res 32:2193–2201PubMedPubMedCentralCrossRefGoogle Scholar
  37. Feng W, D’Urso G (2001) Schizosaccharomyces pombe cells lacking the amino-terminal catalytic domains of DNA polymerase ε are viable but require the DNA damage checkpoint control. Mol Cell Biol 21:4495–4504PubMedPubMedCentralCrossRefGoogle Scholar
  38. Flores-Rozas H, Clark D, Kolodner RD (2000) Proliferating cell nuclear antigen and Msh2p-Msh6p interact to form an active mispair recognition complex. Nat Genet 26:375–378PubMedCrossRefGoogle Scholar
  39. Fridman Y, Gur E, Fleishman SJ, Aharoni A (2013) Computational protein design suggests that human PCNA-partner interactions are not optimized for affinity. Proteins 81:341–348PubMedCrossRefGoogle Scholar
  40. Fujisawa R, Ohashi E, Hirota K, Tsurimoto T (2017) Human CTF18-RFC clamp-loader complexed with non-synthesising DNA polymerase ε efficiently loads the PCNA sliding clamp. Nucleic Acids Res 45(8):4550–4563PubMedPubMedCentralCrossRefGoogle Scholar
  41. Furuya K, Poitelea M, Guo L, Caspari T, Carr AM (2004) Chk1 activation requires Rad9 S/TQ-site phosphorylation to promote association with C-terminal BRCT domains of Rad4TOPBP1. Genes Dev 18:1154–1164PubMedPubMedCentralCrossRefGoogle Scholar
  42. Gali H, Juhasz S, Morocz M, Hajdu I, Fatyol K, Szukacsov V, Burkovics P, Haracska L (2012) Role of SUMO modification of human PCNA at stalled replication fork. Nucleic Acids Res 40:6049–6059PubMedPubMedCentralCrossRefGoogle Scholar
  43. García-Rodríguez LJ, De Piccoli G, Marchesi V, Jones RC, Edmondson RD, Labib K (2015) A conserved Polϵ binding module in Ctf18-RFC is required for S-phase checkpoint activation downstream of Mec1. Nucleic Acids Res 43:8830–8838PubMedPubMedCentralCrossRefGoogle Scholar
  44. Gary R, Ludwig DL, Cornelius HL, MacInnes MA, Park MS (1997) The DNA repair endonuclease XPG binds to proliferating cell nuclear antigen (PCNA) and shares sequence elements with the PCNA-binding regions of FEN-1 and cyclin-dependent kinase inhibitor p21. J Biol Chem 272:24522–24529PubMedCrossRefGoogle Scholar
  45. Gembka A, Toueille M, Smirnova E, Poltz R, Ferrari E, Villani G, Hübscher U (2007) The checkpoint clamp, Rad9-Rad1-Hus1 complex, preferentially stimulates the activity of apurinic/apyrimidinic endonuclease 1 and DNA polymerase beta in long patch base excision repair. Nucleic Acids Res 35:2596–2608PubMedPubMedCentralCrossRefGoogle Scholar
  46. Georgescu RE, Langston L, Yao NY, Yurieva O, Zhang D, Finkelstein J, Agarwal T, O’Donnell ME (2014) Mechanism of asymmetric polymerase assembly at the eukaryotic replication fork. Nat Struct Mol Biol 21:664–670PubMedPubMedCentralCrossRefGoogle Scholar
  47. Georgescu RE, Schauer GD, Yao NY, Langston LD, Yurieva O, Zhang D, Finkelstein J, O’Donnell ME (2015a) Reconstitution of a eukaryotic replisome reveals suppression mechanisms that define leading/lagging strand operation. Elife 4:e04988PubMedPubMedCentralCrossRefGoogle Scholar
  48. Georgescu R, Langston L, O’Donnell M (2015b) A proposal: evolution of PCNA’s role as a marker of newly replicated DNA. DNA Repair (Amst) 29:4–15CrossRefGoogle Scholar
  49. Goellner EM, Smith CE, Campbell CS, Hombauer H, Desai A, Putnam CD, Kolodner RD (2014) PCNA and Msh2-Msh6 activate an Mlh1-Pms1 endonuclease pathway required for Exo1-independent mismatch repair. Mol Cell 55:291–304PubMedPubMedCentralCrossRefGoogle Scholar
  50. Gong Z, Kim JE, Leung CC, Glover JN, Chen J (2010) BACH1/FANCJ acts with TopBP1 and participates early in DNA replication checkpoint control. Mol Cell 37:438–446PubMedPubMedCentralCrossRefGoogle Scholar
  51. Greer DA, Besley BD, Kennedy KB, Davey S (2003) hRad9 rapidly binds DNA containing double-strand breaks and is required for damage-dependent topoisomerase II beta binding protein 1 focus formation. Cancer Res 63:4829–4835PubMedGoogle Scholar
  52. Griffith JD, Lindsey-Boltz LA, Sancar A (2002) Structures of the human Rad17-replication factor C and checkpoint Rad 9-1-1 complexes visualized by glycerol spray/low voltage microscopy. J Biol Chem 277:15233–15236PubMedCrossRefGoogle Scholar
  53. Grushcow JM, Holzen TM, Park KJ, Weinert T, Lichten M, Bishop DK (1999) Saccharomyces cerevisiae checkpoint genes MEC1, RAD17 and RAD24 are required for normal meiotic recombination partner choice. Genetics 153:607–620PubMedPubMedCentralGoogle Scholar
  54. Guo C, Tang TS, Bienko M, Parker JL, Bielen AB, Sonoda E, Takeda S, Ulrich HD, Dikic I, Friedberg EC (2006) Ubiquitin-binding motifs in REV1 protein are required for its role in the tolerance of DNA damage. Mol Cell Biol 26:8892–8900PubMedPubMedCentralCrossRefGoogle Scholar
  55. Hanna JS, Kroll ES, Lundblad V, Spencer FA (2001) Saccharomyces cerevisiae CTF18 and CTF4 are required for sister chromatid cohesion. Mol Cell Biol 21:3144–3158PubMedPubMedCentralCrossRefGoogle Scholar
  56. Havens CG, Walter JC (2009) Docking of a specialized PIP box onto chromatin-bound PCNA creates a Degron for the ubiquitin ligase CRL4Cdt2. Mol Cell 35:93–104PubMedPubMedCentralCrossRefGoogle Scholar
  57. Henneke G, Koundrioukoff S, Hubscher U (2003) Phosphorylation of human Fen1 by cyclin-dependent kinase modulates its role in replication fork regulation. Oncogene 22:4301–4313PubMedCrossRefGoogle Scholar
  58. Hochwagen A, Amon A (2006) Checking your breaks: surveillance mechanisms of meiotic recombination. Curr Biol 16:R217–R228PubMedCrossRefGoogle Scholar
  59. Hoege C, Pfander B, Moldovan GL, Pyrowolakis G, Jentsch S (2002) RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO. Nature 419:135–141PubMedCrossRefGoogle Scholar
  60. Hofmann JFX, Beach D (1994) cdt1 is an essential target of the Cdc10/Sct1 transcription factor: requirement for DNA replication and inhibition of mitosis. EMBO J 13:425–434PubMedPubMedCentralGoogle Scholar
  61. Huang TT, Nijman SM, Mirchandani KD, Galardy PJ, Cohn MA, Haas W, Gygi SP, Ploegh HL, Bernards R, D’Andrea AD (2006) Regulation of monoubiquitinated PCNA by DUB autocleavage. Nat Cell Biol 8:339–347PubMedGoogle Scholar
  62. Iida T, Suetake I, Tajima S, Morioka H, Ohta S, Obuse C, Tsurimoto T (2002) PCNA clamp facilitates action of DNA cytosine methyltransferase 1 on hemimethylated DNA. Genes Cells 7:997–1007PubMedCrossRefGoogle Scholar
  63. Indiani C, O’Donnell M (2006) The replication clamp-loading machine at work in the three domains of life. Nat Rev Mol Cell Biol 7:751–761PubMedCrossRefGoogle Scholar
  64. Indiani C, McInerney P, Georgescu R, Goodman MF, O′Donnell M. (2005) A sliding-clamp tool belt binds high- and low-fidelity DNA polymerases simultaneously. Mol Cell 19:805–815PubMedCrossRefGoogle Scholar
  65. Iyer RR, Pluciennik A, Burdett V, Modrich PL (2006) DNA mismatch repair: functions and mechanisms. Chem Rev 106:302–323PubMedCrossRefGoogle Scholar
  66. Johnson C, Gali VK, Takahashi TS, Kubota T (2016) PCNA retention on DNA into G2/M phase causes genome instability in cells lacking Elg1. Cell Rep 16:684–695PubMedPubMedCentralCrossRefGoogle Scholar
  67. Kadyrov FA, Dzantiev L, Constantin N, Modrich P (2006) Endonucleolytic function of MutLalpha in human mismatch repair. Cell 126:297–308PubMedCrossRefGoogle Scholar
  68. Kadyrov FA, Holmes SF, Arana ME, Lukianova OA, O’Donnell M, Kunkel TA, Modrich P (2007) Saccharomyces cerevisiae MutLalpha is a mismatch repair endonuclease. J Biol Chem 282:37181–37190PubMedPubMedCentralCrossRefGoogle Scholar
  69. Kai M, Wang TS (2003) Checkpoint activation regulates mutagenic translesion synthesis. Genes Dev 17:64–76PubMedPubMedCentralCrossRefGoogle Scholar
  70. Kai M, Furuya K, Paderi F, Carr AM, Wang TS (2007) Rad3-dependent phosphorylation of the checkpoint clamp regulates repair-pathway choice. Nat Cell Biol 9:691–697PubMedCrossRefGoogle Scholar
  71. Karras GI, Fumasoni M, Sienski G, Vanoli F, Branzei D, Jentsch S (2013) Noncanonical role of the 9-1-1 clamp in the error-free DNA damage tolerance pathway. Mol Cell 49:536–546PubMedCrossRefGoogle Scholar
  72. Kaur R, Kostrub CF, Enoch T (2001) Structure-function analysis of fission yeast Hus1-Rad1-Rad9 checkpoint complex. Mol Biol Cell 12:3744–3758PubMedPubMedCentralCrossRefGoogle Scholar
  73. Kawasoe Y, Tsurimoto T, Nakagawa T, Masukata H, Takahashi TS (2016) MutSa maintains the mismatch repair capability by inhibiting PCNA unloading. Elife 5:e15155PubMedPubMedCentralCrossRefGoogle Scholar
  74. Kedar PS, Kim SJ, Robertson A, Hou E, Prasad R, Horton JK, Wilson SH (2002) Direct interaction between mammalian DNA polymerase beta and proliferating cell nuclear antigen. J Biol Chem 277:31115–311123PubMedCrossRefGoogle Scholar
  75. Kelch BA, Makino DL, O’Donnell M, Kuriyan J (2012) Clamp loader ATPases and the evolution of DNA replication machinery. BMC Biol 10:34PubMedPubMedCentralCrossRefGoogle Scholar
  76. Kesti T, Flick K, Keranen S, Syvaoja JE, Wittenberg C (1999) DNA polymerase ε catalytic domains are dispensable for DNA replication, DNA repair, and cell viability. Mol Cell 3:679–685PubMedCrossRefGoogle Scholar
  77. Kim BJ, Lee H (2008) Lys-110 is essential for targeting PCNA to replication and repair foci, and the K110A mutant activates apoptosis. Biol Cell 100:675–686PubMedPubMedCentralCrossRefGoogle Scholar
  78. Kim J, MacNeill SA (2003) Genome stability: a new member of the RFC family. Curr Biol 13:R873–R875PubMedCrossRefGoogle Scholar
  79. Kim SH, Michael WM (2008) Regulated proteolysis of DNA polymerase eta during the DNA-damage response in C. Elegans. Mol Cell 32:757–766PubMedPubMedCentralCrossRefGoogle Scholar
  80. Kim ST, Lim DS, Canman CE, Kastan MB (1999) Substrate specificities and identification of putative substrates of ATM kinase family members. J Biol Chem 274:37538–37543PubMedCrossRefGoogle Scholar
  81. Kim Y, Starostina NG, Kipreos ET (2008) The CRL4Cdt2 ubiquitin ligase targets the degradation of p21Cip1 to control replication licensing. Genes Dev 22:2507–2519PubMedPubMedCentralCrossRefGoogle Scholar
  82. Kleczkowska HE, Marra G, Lettieri T, Jiricny J (2001) hMSH3 and hMSH6 interact with PCNA and colocalize with it to replication foci. Genes Dev 15:724–736PubMedPubMedCentralCrossRefGoogle Scholar
  83. Kobayashi M, Hirano A, Kumano T, Xiang SL, Mihara K, Haseda Y, Matsui O, Shimizu H, Yamamoto K (2004) Critical role for chicken Rad17 and Rad9 in the cellular response to DNA damage and stalled DNA replication. Genes Cells 9:291–303PubMedCrossRefGoogle Scholar
  84. Kochaniak AB, Habuchi S, Loparo JJ, Chang DJ, Cimprich KA, Walter JC, van Oijen AM (2009) Proliferating cell nuclear antigen uses two distinct modes to move along DNA. J Biol Chem 284:17700–117710PubMedPubMedCentralCrossRefGoogle Scholar
  85. Kondo T, Matsumoto K, Sugimoto K (1999) Role of a complex containing Rad17, Mec3, and Ddc1 in the yeast DNA damage checkpoint pathway. Mol Cell Biol 19:1136–1143PubMedPubMedCentralCrossRefGoogle Scholar
  86. Kondo T, Wakayama T, Naiki T, Matsumoto K, Sugimoto K (2001) Recruitment of Mec1 and Ddc1 checkpoint proteins to double-strand breaks through distinct mechanisms. Science 294:867–870PubMedCrossRefGoogle Scholar
  87. Koundrioukoff S, Jónsson ZO, Hasan S, de Jong RN, van der Vliet PC, Hottiger MO, Hübscher U (2000) A direct interaction between proliferating cell nuclear antigen (PCNA) and Cdk2 targets PCNA-interacting proteins for phosphorylation. J Biol Chem 275:22882–22887PubMedCrossRefGoogle Scholar
  88. Krokan HE, Bjørås M (2013) Base excision repair. Cold Spring Harb Perspect Biol 5:a012583PubMedPubMedCentralCrossRefGoogle Scholar
  89. Kubota T, Nishimura K, Kanemaki MT, Donaldson AD (2013a) The Elg1 replication factor C-like complex functions in PCNA unloading during DNA replication. Mol Cell 50:273–280PubMedCrossRefGoogle Scholar
  90. Kubota T, Myung K, Donaldson AD (2013b) Is PCNA unloading the central function of the Elg1/ATAD5 replication factor C-like complex? Cell Cycle 12:2570–2579PubMedPubMedCentralCrossRefGoogle Scholar
  91. Kubota T, Katou Y, Nakato R, Shirahige K, Donaldson AD (2015) Replication-coupled PCNA unloading by the Elg1 complex occurs genome-wide and requires Okazaki fragment ligation. Cell Rep 12:774–787PubMedPubMedCentralCrossRefGoogle Scholar
  92. Kumagai A, Lee J, Yoo HY, Dunphy WG (2006) TopBP1 activates the ATR-ATRIP complex. Cell 124:943–955PubMedCrossRefGoogle Scholar
  93. Kunkel TA, Erie DA (2005) DNA mismatch repair. Annu Rev Biochem 74:681–710PubMedCrossRefGoogle Scholar
  94. Lavin MF (2008) Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer. Nat Rev Mol Cell Biol 9:759–769PubMedCrossRefGoogle Scholar
  95. Lee J, Dunphy WG (2013) The Mre11-Rad50-Nbs1 (MRN) complex has a specific role in the activation of Chk1 in response to stalled replication forks. Mol Biol Cell 24:1343–1353PubMedPubMedCentralCrossRefGoogle Scholar
  96. Lee J, Kumagai A, Dunphy WG (2003a) Claspin, a Chk1-regulatory protein, monitors DNA replication on chromatin independently of RPA, ATR, and Rad17. Mol Cell 11:329–340PubMedCrossRefGoogle Scholar
  97. Lee J, Kumagai A, Dunphy WG (2007) The Rad9-Hus1-Rad1 checkpoint clamp regulates interaction of TopBP1 with ATR. J Biol Chem 282:28036–28044PubMedCrossRefGoogle Scholar
  98. Lee KY, Fu H, Aladjem MI, Myung K (2013) ATAD5 regulates the lifespan of DNA replication factories by modulating PCNA level on the chromatin. J Cell Biol 200:31–44PubMedPubMedCentralCrossRefGoogle Scholar
  99. Lengronne A, McIntyre J, Katou Y, Kanoh Y, Hopfner KP, Shirahige K, Uhlmann F (2006) Establishment of sister chromatid cohesion at the S. Cerevisiae replication fork. Mol Cell 23:787–799PubMedCrossRefGoogle Scholar
  100. Leonhardt H, Rahn HP, Weinzierl P, Sporbert A, Cremer T, Zink D, Cardoso MC (2000) Dynamics of DNA replication factories in living cells. J Cell Biol 149:271–280PubMedPubMedCentralCrossRefGoogle Scholar
  101. Li Z, Pearlman AH, Hsieh P (2016) DNA mismatch repair and the DNA damage response. DNA Repair (Amst) 38:94–101CrossRefGoogle Scholar
  102. Lindsey-Boltz LA, Bermudez VP, Hurwitz J, Sancar A (2001) Purification and characterization of human DNA damage checkpoint Rad complexes. Proc Natl Acad Sci U S A 98:11236–11241PubMedPubMedCentralCrossRefGoogle Scholar
  103. Lindsey-Boltz LA, Kemp MG, Capp C, Sancar A (2015) RHINO forms a stoichiometric complex with the 9-1-1 checkpoint clamp and mediates ATR-Chk1 signaling. Cell Cycle 14:99–108PubMedPubMedCentralCrossRefGoogle Scholar
  104. Longhese MP, Paciotti V, Fraschini R, Zaccarini R, Plevani P, Lucchini G (1997) The novel DNA damage checkpoint protein ddc1p is phosphorylated periodically during the cell cycle and in response to DNA damage in budding yeast. EMBO J 16:5216–5226PubMedPubMedCentralCrossRefGoogle Scholar
  105. López de Saro FJ, O’Donnell M (2001) Interaction of the beta sliding clamp with MutS, ligase, and DNA polymerase I. Proc Natl Acad Sci U S A 98:8376–8380PubMedPubMedCentralCrossRefGoogle Scholar
  106. Lydall D, Nikolsky Y, Bishop DK, Weinert T (1996) A meiotic recombination checkpoint controlled by mitotic checkpoint genes. Nature 383:840–843PubMedCrossRefGoogle Scholar
  107. Maga G, Hübscher U (2003) Proliferating cell nuclear antigen (PCNA): a dancer with many partners. J Cell Sci 116:3051–3060PubMedCrossRefGoogle Scholar
  108. Mailand N, Gibbs-Seymour I, Bekker-Jensen S (2013) Regulation of PCNA-protein interactions for genome stability. Nat Rev Mol Cell Biol 14:269–282PubMedCrossRefGoogle Scholar
  109. Majka J, Burgers PM (2004) The PCNA-RFC families of DNA clamps and clamp loaders. Prog Nucleic Acid Res Mol Biol 78:227–260PubMedCrossRefGoogle Scholar
  110. Majka J, Binz SK, Wold MS, Burgers PM (2006) Replication protein a directs loading of the DNA damage checkpoint clamp to 5′-DNA junctions. J Biol Chem 281:27855–27861PubMedCrossRefGoogle Scholar
  111. Maréchal A, Zou L (2013) DNA damage sensing by the ATM and ATR kinases. Cold Spring Harb Perspect Biol 5:a012716PubMedPubMedCentralCrossRefGoogle Scholar
  112. Marsischky GT, Filosi N, Kane MF, Kolodner R (1996) Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair. Genes Dev 10:407–420PubMedCrossRefGoogle Scholar
  113. Masuda Y, Piao J, Kamiya K (2010) DNA replication-coupled PCNA mono-ubiquitination and polymerase switching in a human in vitro system. J Mol Biol 396:487–500PubMedCrossRefGoogle Scholar
  114. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ (2007) ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 316(5828):1160–1166Google Scholar
  115. Mayer ML, Gygi SP, Aebersold R, Hieter P (2001) Identification of RFC(Ctf18p, Ctf8p, Dcc1p): an alternative RFC complex required for sister chromatid cohesion in S. Cerevisiae. Mol Cell 7:959–970PubMedCrossRefGoogle Scholar
  116. McInerney P, Johnson A, Katz F, O’Donnell M (2007) Characterization of a triple DNA polymerase replisome. Mol Cell 27:527–538PubMedCrossRefGoogle Scholar
  117. Melo JA, Cohen J, Toczyski DP (2001) Two checkpoint complexes are independently recruited to sites of DNA damage in vivo. Genes Dev 15:2809–2821PubMedPubMedCentralGoogle Scholar
  118. Merkle CJ, Karnitz LM, Henry-Sánchez JT, Chen J (2003) Cloning and characterization of hCTF18, hCTF8, and hDCC1. Human homologs of a Saccharomyces cerevisiae complex involved in sister chromatid cohesion establishment. J Biol Chem 278:30051–30056PubMedCrossRefGoogle Scholar
  119. Moldovan GL, Pfander B, Jentsch S (2006) PCNA controls establishment of sister chromatid cohesion during S phase. Mol Cell 23:723–732PubMedCrossRefGoogle Scholar
  120. Moldovan GL, Pfander B, Jentsch S (2007) PCNA, the maestro of the replication fork. Cell 129:665–679PubMedCrossRefGoogle Scholar
  121. Moldovan GL, Dejsuphong D, Petalcorin MI, Hofmann K, Takeda S, Boulton SJ, D’Andrea AD (2012) Inhibition of homologous recombination by the PCNA-interacting protein PARI. Mol Cell 45:75–86PubMedCrossRefGoogle Scholar
  122. Mordes DA, Glick GG, Zhao R, Cortez D (2008) TopBP1 activates ATR through ATRIP and a PIKK regulatory domain. Genes Dev 22:1478–1489PubMedPubMedCentralCrossRefGoogle Scholar
  123. Mortusewicz O, Schermelleh L, Walter J, Cardoso MC, Leonhardt H (2005) Recruitment of DNA methyltransferase I to DNA repair sites. Proc Natl Acad Sci U S A 102:8905–8909PubMedPubMedCentralCrossRefGoogle Scholar
  124. Murakami T, Takano R, Takeo S, Taniguchi R, Ogawa K, Ohashi E, Tsurimoto T (2010) Stable interaction between the human proliferating cell nuclear antigen loader complex Ctf18-replication factor C (RFC) and DNA polymerase ε is mediated by the cohesion-specific subunits, Ctf18, Dcc1, and Ctf8. J Biol Chem 285:34608–34615PubMedPubMedCentralCrossRefGoogle Scholar
  125. Naiki T, Kondo T, Nakada D, Matsumoto K, Sugimoto K (2001) Chl12 (Ctf18) forms a novel replication factor C-related complex and functions redundantly with Rad24 in the DNA replication checkpoint pathway. Mol Cell Biol 21:5838–5845PubMedPubMedCentralCrossRefGoogle Scholar
  126. Navadgi-Patil VM, Burgers PM (2008) Yeast DNA replication protein Dpb11 activates the Mec1/ATR checkpoint kinase. J Biol Chem 283:35853–35859PubMedPubMedCentralCrossRefGoogle Scholar
  127. Navadgi-Patil VM, Burgers PM (2009) The unstructured C-terminal tail of the 9-1-1 clamp subunit Ddc1 activates Mec1/ATR via two distinct mechanisms. Mol Cell 36:743–753PubMedPubMedCentralCrossRefGoogle Scholar
  128. Nishino K, Inoue E, Takada S, Abe T, Akita M, Yoshimura A, Tada S, Kobayashi M, Yamamoto K, Seki M, Enomoto T (2008) A novel role for Rad17 in homologous recombination. Genes Genet Syst 83:427–431PubMedCrossRefGoogle Scholar
  129. Nishitani H, Sugimoto N, Roukos V, Nakanishi Y, Saijo M, Obuse C, Tsurimoto T, Nakayama KI, Nakayama K, Fujita M, Lygerou Z, Nishimoto T (2006) Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdt1 for proteolysis. EMBO J 25:1126–1136PubMedPubMedCentralCrossRefGoogle Scholar
  130. Nishitani H, Shiomi Y, Iida H, Michishita M, Takami T, Tsurimoto T (2008) CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4-DDB1Cdt2 pathway during S phase and after UV irradiation. J Biol Chem 283:29045–29052PubMedPubMedCentralCrossRefGoogle Scholar
  131. O’Donnell M, Li H (2016) The eukaryotic replisome goes under the microscope. Curr Biol 26:R247–R256PubMedPubMedCentralCrossRefGoogle Scholar
  132. Ohashi E, Takeishi Y, Ueda S, Tsurimoto T (2014) Interaction between Rad9-Hus1-Rad1 and TopBP1 activates ATR-ATRIP and promotes TopBP1 recruitment to sites of UV-damage. DNA Repair (Amst) 21:1–11CrossRefGoogle Scholar
  133. O’Neill T, Dwyer AJ, Ziv Y, Chan DW, Lees-Miller SP, Abraham RH, Lai JH, Hill D, Shiloh Y, Cantley LC, Rathbun GA (2000) Utilization of oriented peptide libraries to identify substrate motifs selected by ATM. J Biol Chem 275:22719–22727PubMedCrossRefGoogle Scholar
  134. Pandita RK, Sharma GG, Laszlo A, Hopkins KM, Davey S, Chakhparonian M, Gupta A, Wellinger RJ, Zhang J, Powell SN, Roti Roti JL, Lieberman HB, Pandita TK (2006) Mammalian Rad9 plays a role in telomere stability, S- and G2-phase-specific cell survival, and homologous recombinational repair. Mol Cell Biol 26:1850–1864PubMedPubMedCentralCrossRefGoogle Scholar
  135. Park SY, Jeong MS, Han CW, Yu HS, Jang SB (2016) Structural and functional insight into proliferating cell nuclear antigen. J Microbiol Biotechnol 26:637–647PubMedCrossRefGoogle Scholar
  136. Parnas O, Zipin-Roitman A, Pfander B, Liefshitz B, Mazor Y, Ben-Aroya S, Jentsch S, Kupiec M (2010) Elg1, an alternative subunit of the RFC clamp loader, preferentially interacts with SUMOylated PCNA. EMBO J 29:2611–2622PubMedPubMedCentralCrossRefGoogle Scholar
  137. Paulovich AG, Armour CD, Hartwell LH (1998) The Saccharomyces cerevisiae RAD9, RAD17, RAD24 and MEC3 genes are required for tolerating irreparable, ultraviolet-induced DNA damage. Genetics 150:75–93PubMedPubMedCentralGoogle Scholar
  138. Pluciennik A, Dzantiev L, Iyer RR, Constantin N, Kadyrov FA, Modrich P (2010) PCNA function in the activation and strand direction of MutLα endonuclease in mismatch repair. Proc Natl Acad Sci U S A 107:16066–16071PubMedPubMedCentralCrossRefGoogle Scholar
  139. Prelich G, Stillman B (1988) Coordinated leading and lagging strand synthesis during SV40 DNA replication in vitro requires PCNA. Cell 53:117–126PubMedCrossRefGoogle Scholar
  140. Prelich G, Kostura M, Marshak DR, Mathews MB, Stillman B (1987) The cell-cycle regulated proliferating cell nuclear antigen is required for SV40 DNA replication in vitro. Nature 326:471–475PubMedCrossRefGoogle Scholar
  141. Prindle MJ, Loeb LA (2012) DNA polymerase delta in DNA replication and genome maintenance. Environ Mol Mutagen 53:666–682PubMedPubMedCentralCrossRefGoogle Scholar
  142. Puddu F, Granata M, Di Nola L, Balestrini A, Piergiovanni G, Lazzaro F, Giannattasio M, Plevani P, Muzi-Falconi M (2008) Phosphorylation of the budding yeast 9-1-1 complex is required for Dpb11 function in the full activation of the UV-induced DNA damage checkpoint. Mol Cell Biol 28:4782–4793PubMedPubMedCentralCrossRefGoogle Scholar
  143. Pursell ZF, Isoz I, Lundström EB, Johansson E, Kunkel TA (2007) Yeast DNA polymerase epsilon participates in leading-strand DNA replication. Science 317:127–130PubMedPubMedCentralCrossRefGoogle Scholar
  144. Rappas M, Oliver AW, Pearl LH (2011) Structure and function of the Rad9-binding region of the DNA-damage checkpoint adaptor TopBP1. Nucleic Acids Res 39:313–324PubMedCrossRefGoogle Scholar
  145. Roos-Mattjus P, Vroman BT, Burtelow MA, Rauen M, Eapen AK, Karnitz LM (2002) Genotoxin-induced Rad9-Hus1-Rad1 (9-1-1) chromatin association is an early checkpoint signaling event. J Biol Chem 277:43809–43812PubMedCrossRefGoogle Scholar
  146. Roos-Mattjus P, Hopkins KM, Oestreich AJ, Vroman BT, Johnson KL, Naylor S, Lieberman HB, Karnitz LM (2003) Phosphorylation of human Rad9 is required for genotoxin-activated checkpoint signaling. J Biol Chem 278:24428–24437PubMedCrossRefGoogle Scholar
  147. Rousseau D, Cannella D, Boulaire J, Fitzgerald P, Fotedar A, Fotedar R (1999) Growth inhibition by CDK-cyclin and PCNA binding domains of p21 occurs by distinct mechanisms and is regulated by ubiquitin-proteasome pathway. Oncogene 18:4313–4325PubMedCrossRefGoogle Scholar
  148. Rudra S, Skibbens RV (2013) Cohesin codes - interpreting chromatin architecture and the many facets of cohesin function. J Cell Sci 126:31–41PubMedPubMedCentralCrossRefGoogle Scholar
  149. Sabbioneda S, Minesinger BK, Giannattasio M, Plevani P, Muzi-Falconi M, Jinks-Robertson S (2005) The 9-1-1 checkpoint clamp physically interacts with polzeta and is partially required for spontaneous polzeta-dependent mutagenesis in Saccharomyces cerevisiae. J Biol Chem 280:38657–38665PubMedCrossRefGoogle Scholar
  150. Saberi A, Nakahara M, Sale JE, Kikuchi K, Arakawa H, Buerstedde JM, Yamamoto K, Takeda S, Sonoda E (2008) The 9-1-1 DNA clamp is required for immunoglobulin gene conversion. Mol Cell Biol 28:6113–6122PubMedPubMedCentralCrossRefGoogle Scholar
  151. Sancar A, Lindsey-Boltz LA, Unsal-Kaçmaz K, Linn S (2004) Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem 73:39–85PubMedCrossRefGoogle Scholar
  152. Shibahara K, Stillman B (1999) Replication-dependent marking of DNA by PCNA facilitates CAF-1-coupled inheritance of chromatin. Cell 96:575–585PubMedCrossRefGoogle Scholar
  153. Shibutani ST, de la Cruz AF, Tran V, Turbyfill WJ 3rd, Reis T, Edgar BA, Duronio RJ (2008) Intrinsic negative cell cycle regulation provided by PIP box- and Cul4Cdt2-mediated destruction of E2f1 during S phase. Dev Cell 15:890–900PubMedPubMedCentralCrossRefGoogle Scholar
  154. Shinohara M, Sakai K, Ogawa T, Shinohara A (2003) The mitotic DNA damage checkpoint proteins Rad17 and Rad24 are required for repair of double-strand breaks during meiosis in yeast. Genetics 164:855–865PubMedPubMedCentralGoogle Scholar
  155. Shiomi Y, Nishitani H (2013) Alternative replication factor C protein, Elg1, maintains chromosome stability by regulating PCNA levels on chromatin. Genes Cells 18:946–959PubMedCrossRefGoogle Scholar
  156. Shiomi Y, Nishitani H (2017) Control of genome integrity by RFC complexes; conductors of PCNA loading onto and unloading from chromatin during DNA replication. Genes (Basel) 8., pii:E52CrossRefGoogle Scholar
  157. Shiomi Y, Shinozaki A, Nakada D, Sugimoto K, Usukura J, Obuse C, Tsurimoto T (2002) Clamp and clamp loader structures of the human checkpoint protein complexes, Rad9-1-1 and Rad17-RFC. Genes Cells 7:861–868PubMedCrossRefGoogle Scholar
  158. Shiomi Y, Shinozaki A, Sugimoto K, Usukura J, Obuse C, Tsurimoto T (2004) The reconstituted human Chl12-RFC complex functions as a second PCNA loader. Genes Cells 9:279–290PubMedCrossRefGoogle Scholar
  159. Shiomi Y, Hayashi A, Ishii T, Shinmyozu K, Nakayama J, Sugasawa K, Nishitani H (2012) Two different replication factor C proteins, Ctf18 and RFC1, separately control PCNA-CRL4Cdt2-mediated Cdt1 proteolysis during S phase and following UV irradiation. Mol Cell Biol 32:2279–2288PubMedPubMedCentralCrossRefGoogle Scholar
  160. Sirbu BM, McDonald WH, Dungrawala H, Badu-Nkansah A, Kavanaugh GM, Chen Y, Tabb DL, Cortez D (2013) Identification of proteins at active, stalled, and collapsed replication forks using isolation of proteins on nascent DNA (iPOND) coupled with mass spectrometry. J Biol Chem 288:31458–31467PubMedPubMedCentralCrossRefGoogle Scholar
  161. Skibbens RV (2009) Establishment of sister chromatid cohesion. Curr Biol 19:R1126–R1132PubMedPubMedCentralCrossRefGoogle Scholar
  162. Smith LA, Makarova AV, Samson L, Thiesen KE, Dhar A, Bessho T (2012) Bypass of a psoralen DNA interstrand cross-link by DNA polymerases β, ι, and κ in vitro. Biochemistry 51:8931–8938PubMedPubMedCentralCrossRefGoogle Scholar
  163. St Onge RP, Udell CM, Casselman R, Davey S (1999) The human G2 checkpoint control protein hRAD9 is a nuclear phosphoprotein that forms complexes with hRAD1 and hHUS1. Mol Biol Cell 10:1985–1995PubMedCrossRefGoogle Scholar
  164. St Onge RP, Besley BD, Park M, Casselman R, Davey S (2001) DNA damage-dependent and -independent phosphorylation of the hRad9 checkpoint protein. J Biol Chem 276:41898–41905PubMedCrossRefGoogle Scholar
  165. St Onge RP, Besley BD, Pelley JL, Davey S (2003) A role for the phosphorylation of hRad9 in checkpoint signaling. J Biol Chem 278:26620–26628PubMedCrossRefGoogle Scholar
  166. Stelter P, Ulrich HD (2003) Control of spontaneous and damage-induced mutagenesis by SUMO and ubiquitin conjugation. Nature 425:188–191PubMedCrossRefGoogle Scholar
  167. Subramanian VV, Hochwagen A (2014) The meiotic checkpoint network: step-by-step through meiotic prophase. Cold Spring Harb Perspect Biol 6:a016675PubMedPubMedCentralCrossRefGoogle Scholar
  168. Sun Q, Tsurimoto T, Juillard F, Li L, Li S, De León VE, Chen S, Kaye K (2014) Kaposi’s sarcoma-associated herpesvirus LANA recruits the DNA polymerase clamp loader to mediate efficient replication and virus persistence. Proc Natl Acad Sci U S A 111:11816–11821PubMedPubMedCentralCrossRefGoogle Scholar
  169. Takeishi Y, Ohashi E, Ogawa K, Masai H, Obuse C, Tsurimoto T (2010) Casein kinase 2-dependent phosphorylation of human Rad9 mediates the interaction between human Rad9-Hus1-Rad1 complex and TopBP1. Genes Cells 15:761–771PubMedCrossRefGoogle Scholar
  170. Takeishi Y, Iwaya-Omi R, Ohashi E, Tsurimoto T (2015) Intramolecular binding of the Rad9 C terminus in the checkpoint clamp Rad9-Hus1-Rad1 is closely linked with its DNA binding. J Biol Chem 290:19923–19932PubMedPubMedCentralCrossRefGoogle Scholar
  171. Terai K, Abbas T, Jazaeri AA, Dutta A (2010) CRL4(Cdt2) E3 ubiquitin ligase monoubiquitinates PCNA to promote translesion DNA synthesis. Mol Cell 37:143–149PubMedPubMedCentralCrossRefGoogle Scholar
  172. Terret ME, Sherwood R, Rahman S, Qin J, Jallepalli PV (2009) Cohesin acetylation speeds the replication fork. Nature 462:231–234PubMedPubMedCentralCrossRefGoogle Scholar
  173. Thompson DA, Stahl FW (1999) Genetic control of recombination partner preference in yeast meiosis. Isolation and characterization of mutants elevated for meiotic unequal sister-chromatid recombination. Genetics 153:621–641PubMedPubMedCentralGoogle Scholar
  174. Tinker RL, Kassavetis GA, Geiduschek EP (1994) Detecting the ability of viral, bacterial and eukaryotic proteins to track along DNA. EMBO J 13:5330–5337PubMedPubMedCentralGoogle Scholar
  175. Tsurimoto T (1999) PCNA binding proteins. Front Biosci 4:D849–D858PubMedCrossRefGoogle Scholar
  176. Tsurimoto T, Stillman B (1989) Purification of a cellular replication factor, RF-C, that is required for coordinated synthesis of leading and lagging strands during simian virus 40 DNA replication in vitro. Mol Cell Biol 9:609–619PubMedPubMedCentralCrossRefGoogle Scholar
  177. Ueda S, Takeishi Y, Ohashi E, Tsurimoto T (2012) Two serine phosphorylation sites in the C-terminus of Rad9 are critical for 9-1-1 binding to TopBP1 and activation of the DNA damage checkpoint response in HeLa cells. Genes Cells 17:807–816PubMedCrossRefGoogle Scholar
  178. Ulrich HD (2013) New insights into replication clamp unloading. J Mol Biol 425:4727–4732PubMedCrossRefGoogle Scholar
  179. Ulrich HD, Jentsch S (2000) Two RING finger proteins mediate cooperation between ubiquitinconjugating enzymes in DNA repair. EMBO J 19:3388–3397PubMedPubMedCentralCrossRefGoogle Scholar
  180. Volkmer E, Karnitz LM (1999) Human homologs of Schizosaccharomyces pombe rad1, hus1, and rad9 form a DNA damage-responsive protein complex. J Biol Chem 274:567–570PubMedCrossRefGoogle Scholar
  181. Waga S, Stillman B (1998) The DNA replication fork in eukaryotic cells. Annu Rev Biochem 67:721–751PubMedCrossRefGoogle Scholar
  182. Waga S, Hannon GJ, Beach D, Stillman B (1994) The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature 369:574–578PubMedCrossRefGoogle Scholar
  183. Wang X, Zou L, Zheng H, Wei Q, Elledge SJ, Li L (2003) Genomic instability and endoreduplication triggered by RAD17 deletion. Genes Dev 17:965–970PubMedPubMedCentralCrossRefGoogle Scholar
  184. Wang X, Hu B, Weiss RS, Wang Y (2006) The effect of Hus1 on ionizing radiation sensitivity is associated with homologous recombination repair but is independent of nonhomologous end-joining. Oncogene 25:1980–1983PubMedCrossRefGoogle Scholar
  185. Warbrick E, Lane DP, Glover DM, Cox LS (1995) A small peptide inhibitor of DNA replication defines the site of interaction between the cyclin-dependent kinase inhibitor p21waf1 and the proliferating cell nuclear antigen. Curr Biol 5:275–282PubMedCrossRefGoogle Scholar
  186. Weiss RS, Matsuoka S, Elledge SJ, Leder P (2002) Hus1 acts upstream of chk1 in a mammalian DNA damage response pathway. Curr Biol 12:73–77PubMedCrossRefGoogle Scholar
  187. Wu X, Shell SM, Zou Y (2005) Interaction and colocalization of Rad9/Rad1/Hus1 checkpoint complex with replication protein a in human cells. Oncogene 24:4728–4735PubMedPubMedCentralCrossRefGoogle Scholar
  188. Xiong Y, Hannon GJ, Zhang H, Casso D, Kobayashi R, Beach D (1993) p21 is a universal inhibitor of cyclin kinases. Nature 366:701–704PubMedCrossRefGoogle Scholar
  189. Xu X, Vaithiyalingam S, Glick GG, Mordes DA, Chazin WJ, Cortez D (2008) The basic cleft of RPA70N binds multiple checkpoint proteins, including RAD9, to regulate ATR signaling. Mol Cell Biol 28:7345–7353PubMedPubMedCentralCrossRefGoogle Scholar
  190. Yan S, Michael WM (2009) TopBP1 and DNA polymerase-alpha directly recruit the 9-1-1 complex to stalled DNA replication forks. J Cell Biol 184:793–804PubMedPubMedCentralCrossRefGoogle Scholar
  191. Yao NY, O’Donnell M (2012) The RFC clamp loader: structure and function. Subcell Biochem 62:259–279PubMedPubMedCentralCrossRefGoogle Scholar
  192. Yao N, Turner J, Kelman Z, Stukenberg PT, Dean F, Shechter D, Pan ZQ, Hurwitz J, O’Donnell M (1996) Clamp loading, unloading and intrinsic stability of the PCNA, beta and gp45 sliding clamps of human, E. Coli and T4 replicases. Genes Cells 1:101–113PubMedCrossRefGoogle Scholar
  193. You Z, Kong L, Newport J (2002) The role of single-stranded DNA and polymerase alpha in establishing the ATR, Hus1 DNA replication checkpoint. J Biol Chem 277:27088–27093PubMedCrossRefGoogle Scholar
  194. Yu C, Gan H, Han J, Zhou ZX, Jia S, Chabes A, Farrugia G, Ordog T, Zhang Z (2014) Strand-specific analysis shows protein binding at replication forks and PCNA unloading from lagging strands when forks stall. Mol Cell 56:551–563PubMedPubMedCentralCrossRefGoogle Scholar
  195. Zamir L, Zaretsky M, Fridman Y, Ner-Gaon H, Rubin E, Aharoni A (2012) Tight coevolution of proliferating cell nuclear antigen (PCNA)-partner interaction networks in fungi leads to interspecies network incompatibility. Proc Natl Acad Sci U S A 109:E406–E414PubMedPubMedCentralCrossRefGoogle Scholar
  196. Zhang H, Xiong Y, Beach D (1993) Proliferating cell nuclear antigen and p21 are components of multiple cell cycle kinase complexes. Mol Biol Cell 4:897–906PubMedPubMedCentralCrossRefGoogle Scholar
  197. Zhang Z, Shibahara K, Stillman B (2000) PCNA connects DNA replication to epigenetic inheritance in yeast. Nature 408:221–225PubMedCrossRefGoogle Scholar
  198. Zou L, Cortez D, Elledge SJ (2002) Regulation of ATR substrate selection by Rad17-dependent loading of Rad9 complexes onto chromatin. Genes Dev 16:198–208PubMedPubMedCentralCrossRefGoogle Scholar
  199. Zou L, Liu D, Elledge SJ (2003) Replication protein A-mediated recruitment and activation of Rad17 complexes. Proc Natl Acad Sci U S A 100:13827–11383PubMedPubMedCentralCrossRefGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  1. 1.Department of Biology, Faculty of ScienceKyushu UniversityFukuokaJapan

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