The S-phase checkpoint: Targeting the replication fork

Biology of the Cell

Volumn 101, Issue 11, 2009, Pages 617-627

  Segurado, Mónica ^a   Tercero, José Antonio ^a  

^a CENTRO DE BIOLOGÍA MOLECULAR SEVERO OCHOA   (Spain)

Author keywords

Budding yeast (Saccharomyces cerevisiae); Checkpoint; Chromosome replication; Genome stability; Replication fork integrity

Indexed keywords

ATM PROTEIN; CHECKPOINT KINASE 2;

CELL CYCLE ARREST; CELL CYCLE S PHASE; CELL SURVIVAL; CELL VIABILITY; CELLULAR STRESS RESPONSE; DNA DAMAGE; DNA REPLICATION; GENE EXPRESSION; GENE FUNCTION; GENE TARGETING; GENOMIC INSTABILITY; HUMAN; PRIORITY JOURNAL; REVIEW; SACCHAROMYCES CEREVISIAE;

CELL CYCLE PROTEINS; DNA REPLICATION; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; PROTEIN-SERINE-THREONINE KINASES; S PHASE; SACCHAROMYCES CEREVISIAE; SACCHAROMYCES CEREVISIAE PROTEINS;

SACCHAROMYCES CEREVISIAE; SACCHAROMYCETALES;

EID: 70350103981     PISSN: 02484900     EISSN: 1768322X     Source Type: Journal    
DOI: 10.1042/BC20090053     Document Type: Review

References (109)

1. Admire, A., Shanks, L., Danzl, N., Wang, M., Weier, U., Stevens, W., Hunt, E. and Weinert, T. (2006) Cycles of chromosome instability are associated with a fragile site and are increased by defects in DNA replication and checkpoint controls in yeast. Genes Dev. 20, 159-173
2. Aguilera, A. and Gomez-Gonzalez, B. (2008) Genome instability: a mechanistic view of its causes and consequences. Nat. Rev. Genet. 9, 204-217
3. Alcasabas, A.A., Osborn, A.J., Bachant, J., Hu, F., Werler, P.J., Bousset, K., Furuya, K., Diffley, J.F.X., Carr, A.M. and Elledge, S.J. (2001) Mrc1 transduces signals of DNA replication stress to activate Rad53. Nat. Cell. Biol. 3, 958-965
4. Allen, J.B., Zhou, Z., Siede, W., Friedberg, E.C. and Elledge, S.J. (1994) The SAD1/RAD53 protein kinase controls multiple checkpoints and DNA damage-induced transcription in yeast. Genes Dev. 8, 2401-2415
5. Arlt, M.F., Durkin, S.G., Ragland, R.L. and Glover, T.W. (2006) Common fragile sites as targets for chromosome rearrangements. DNA Repair (Amsterdam) 5, 1126-1135
6. Bailis, J.M., Luche, D.D., Hunter, T. and Forsburg, S.L. (2008) Minichromosome maintenance proteins interact with checkpoint and recombination proteins to promote S-phase genome stability. Mol. Cell. Biol. 28, 1724-1738
7. Binz, S.K., Sheehan, A.M. and Wold, M.S. (2004) Replication protein A phosphorylation and the cellular response to DNA damage. DNA Repair (Amsterdam) 3, 1015-1024
8. Boddy, M.N. and Russell, P. (2001) DNA replication checkpoint. Curr. Biol. 11, R953-956
9. Boddy, M.N., Furnari, B., Mondesert, O. and Russell, P. (1998) Replication checkpoint enforced by kinases Cds1 and Chk1. Science 280, 909-912
10. Boddy, M.N., Shanahan, P., McDonald, W.H., Lopez-Girona, A., Noguchi, E., Yates, I.J. and Russell, P. (2003) Replication checkpoint kinase Cds1 regulates recombinational repair protein Rad60. Mol. Cell. Biol. 23, 5939-5946
11. Branzei, D. and Foiani, M. (2007) Interplay of replication checkpoints and repair proteins at stalled replication forks. DNA Repair (Amst) 6, 994-1003
12. Branzei, D. and Foiani, M. (2008) Regulation of DNA repair throughout the cell cycle. Nat. Rev. Mol. Cell. Biol. 9, 297-308
13. Branzei, D., Sollier, J., Liberi, G., Zhao, X., Maeda, D., Seki, M., Enomoto, T., Ohta, K. and Foiani, M. (2006) Ubc9- and mms21-mediated sumoylation counteracts recombinogenic events at damaged replication forks. Cell 127, 509-522
14. Branzei, D., Vanoli, F. and Foiani, M. (2008) SUMOylation regulates Rad18-mediated template switch. Nature 456, 915-920
15. Brondello, J.M., Boddy, M.N., Furnari, B. and Russell, P. (1999) Basis for the checkpoint signal specificity that regulates Chk1 and Cds1 protein kinases. Mol. Cell. Biol. 19, 4262-4269
16. Brown, E.J. and Baltimore, D. (2000) ATR disruption leads to chromosomal fragmentation and early embryonic lethality. Genes Dev. 14, 397-402
17. Brown, E.J. and Baltimore, D. (2003) Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance. Genes Dev. 17, 615-628
18. Brush, G.S., Morrow, D.M., Hieter, P. and Kelly, T.J. (1996) The ATM homolog MEC1 i s required for phosphorylation of replication protein A in yeast. Proc. Natl. Acad. Sci. U.S.A. 93, 15075-15080
19. Byun, T.S., Pacek, M., Yee, M.C., Walter, J.C. and Cimprich, K.A. (2005) Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint. Genes Dev. 19, 1040-1052
20. Calzada, A., Hodgson, B., Kanemaki, M., Bueno, A. and Labib, K. (2005) Molecular anatomy and regulation of a stable replisome at a paused eukaryotic DNA replication fork. Genes Dev. 19, 1905-1919
21. Casper, A.M., Nghiem, P., Arlt, M.F. and Glover, T.W. (2002) ATR regulates fragile site stability. Cell 111, 779-789
22. Cha, R.S. and Kleckner, N. (2002) ATR homolog Mec1 promotes fork progression, thus averting breaks in replication slow zones. Science 297, 602-606
23. Chin, J.K., Bashkirov, V.I., Heyer, W.D. and Romesberg, F.E. (2006) Esc4/ Rtt107 and the control of recombination during replication. DNA Repair (Amst) 5, 618-628
24. Cobb, J.A., Bjergbaek, L., Shimada, K., Frei, C. and Gasser, S.M. (2003) DNA polymerase stabilization at stalled replication forks requires Mec1 and the RecQ helicase Sgs1, EMBO J. 22, 4325-4336
25. Cobb, J.A., Schleker, T., Rojas, V., Bjergbaek, L., Tercero, J.A. and Gasser, S.M. (2005) Replisome instability, fork collapse, and gross chromosomal rearrangements arise synergistically from Mec1 kinase and RecQ helicase mutations. Genes Dev. 19, 3055-3069
26. Cortez, D., Glick, G. and Elledge, S.J. (2004) Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases. Proc. Natl. Acad. Sci. U.S.A. 101, 10078-10083
27. Cotta-Ramusino, C., Fachinetti, D., Lucca, C., Doksani, Y., Lopes, M., Sogo, J. and Foiani, M. (2005) Exo1 processes stalled replication forks and counteracts fork reversal in checkpoint-defective cells. Mol. Cell 17, 153-159
28. Desany, B.A., Alcasabas, A.A., Bachant, J.B. and Elledge, S.J. (1998) Recovery from DNA replicational stress is the essential function of the S-phase checkpoint pathway. Genes Dev. 12, 2956-2970
29. Doksani, Y, Bermejo, R., Fiorani, S., Haber, J.E. and Foiani, M. (2009) Replicon dynamics, dormant origin firing, and terminal fork integrity after double-strand break formation. Cell 137, 247-258
30. Feng, W., Collingwood, D., Boeck, M.E., Fox, L.A., Alvino, G.M., Fangman, W.L., Raghuraman, M.K. and Brewer, B.J. (2006) Genomic mapping of single-stranded DNA in hydroxyurea-challenged yeasts identifies origins of replication. Nat. Cell. Biol. 8, 148-155
31. Friedberg, E.C. (2003) DNA damage and repair. Nature 421, 436-440
32. Friedel, A.M., Pike, B.L. and Gasser, S.M. (2009) ATR/Mec1: coordinating fork stability and repair, Curr. Opin. Cell. Biol. 21, 237-244
33. Froget, B., Blaisonneau, J., Lambert, S. and Baldacci, G. (2008) Cleavage of stalled forks by fission yeast Mus81/Eme1 in absence of DNA replication checkpoint. Mol. Biol. Cell 19, 445-456
34. Gardner, R., Putnam, C.W. and Weinert, T. (1999) RAD53, DUN1 and PDS1 define two parallel G2/M checkpoint pathways in budding yeast. EMBO J. 18, 3173-3185
35. Han, J., Zhou, H., Li, Z., Xu, R.M. and Zhang, Z. (2007) Acetylation of lysine 56 of histone H3 catalyzed by Rtt109 and regulated by Asf1 is required for replisome integrity. J. Biol. Chem. 282, 28587-28596
36. Harrison, J.C. and Haber, J.E. (2006) Surviving the breakup: the DNA damage checkpoint. Annu. Rev. Genet. 40, 209-235
37. Hoeijmakers, J.H. (2001) Genome maintenance mechanisms for preventing cancer. Nature 411, 366-374
38. Ishimi, Y., Komamura-Kohno, Y., Kwon, H.J., Yamada, K. and Nakanishi, M. (2003) Identification of MCM4 as a target of the DNA replication block checkpoint system. J. Biol. Chem. 278, 24644-24650
39. Jia, X., Weinert, T. and Lydall, D. (2004) Mec1 and Rad53 inhibit formation of single-stranded DNA at telomeres of Saccharomyces cerevisiae cdc13-1 mutants. Genetics 166, 753-764
40. Kai, M., Boddy, M.N., Russell, P. and Wang, T.S. (2005) Replication checkpoint kinase Cds1 regulates Mus81 to preserve genome integrity during replication stress. Genes Dev. 19, 919-932
41. Kai, M., Furuya, K., Paderi, F., Carr, A.M. and Wang, T.S. (2007) Rad3-dependent phosphorylation of the checkpoint clamp regulates repair-pathway choice. Nat. Cell. Biol. 9, 691-697
42. Katou, Y., Kanoh, Y., Bando, M., Noguchi, H., Tanaka, H., Ashikari, T., Sugimoto, K. and Shirahige, K. (2003) S-phase checkpoint proteins Tof1 and Mrc1 form a stable replication-pausing complex. Nature 424, 1078-1083
43. Kolodner, R.D., Putnam, C.D. and Myung, K. (2002) Maintenance of genome stability in Saccharomyces cerevisiae. Science 297, 552-557
44. Labib, K., Tercero, J.A. and Diffley, J.F. (2000) Uninterrupted MCM2-7 function required for DNA replication fork progression. Science 288, 1643-1647
45. Lahiri, M., Gustafson, T.L., Majors, E.R. and Freudenreich, C.H. (2004) Expanded CAG repeats activate the DNA damage checkpoint pathway. Mol. Cell 15, 287-293
46. Lambert, S., Froget, B. and Carr, A.M. (2007) Arrested replication fork processing: interplay between checkpoints and recombination. DNA Repair (Amsterdam) 6, 1042-1061
47. Lambert, S., Watson, A., Sheedy, D.M., Martin, B. and Carr, A.M. (2005) Gross chromosomal rearrangements and elevated recombination at an inducible site-specific replication fork barrier. Cell 121, 689-702
48. Lemoine, F.J., Degtyareva, N.P., Lobachev, K. and Petes, T.D. (2005) Chromosomal translocations in yeast induced by low levels of DNA polymerase a model for chromosome fragile sites. Cell 120, 587-598
49. Lindsay, H.D., Griffiths, D.J., Edwards, R.J., Christensen, P.U., Murray, J.M., Osman, F., Walworth, N. and Carr, A.M. (1998) S-phase-specific activation of Cds1 kinase defines a subpathway of the checkpoint response in Schizosaccharomyces pombe. Genes Dev. 12, 382-395
50. Lisby, M., Barlow, J.H., Burgess, R.C. and Rothstein, R. (2004) Choreography of the DNA damage response: spatiotemporal relationships among checkpoint and repair proteins. Cell 118, 699-713
51. Liu, Q., Guntuku, S., Cui, X.S., Matsuoka, S., Cortez, D., Tamai, K., Luo, G., Carattini-Rivera, S., DeMayo, F., Bradley, A. et al. (2000) Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint. Genes Dev. 14, 1448-1459
52. Lopes, M., Cotta-Ramusino, C., Pellicioli, A., Liberi, G., Plevani, P., Muzi-Falconi, M., Newlon, C. and Foiani, M. (2001) The DNA replication checkpoint response stabilizes stalled replication forks. Nature 412, 557-561
53. Lopes, M., Cotta-Ramusino, C., Liberi, G. and Foiani, M. (2003) Branch migrating sister chromatid junctions form at replication origins through Rad51/Rad52-independent mechanisms. Mol. Cell 12, 1499-1510
54. Lucca, C., Vanoli, F., Cotta-Ramusino, C., Pellicioli, A., Liberi, G., Haber, J. and Foiani, M. (2004) Checkpoint-mediated control of replisome-fork association and signalling in response to replication pausing. Oncogene 23, 1206-1213
55. Lupardus, P.J., Byun, T., Yee, M.C., Hekmat-Nejad, M. and Cimprich, K.A. (2002) A requirement for replication in activation of the ATR-dependent DNA damage checkpoint. Genes Dev. 16, 2327-2332
56. Martinho, R.G., Lindsay, H.D., Flaggs, G., DeMaggio, A.J., Hoekstra, M.F., Carr, A.M. and Bentley, N.J. (1998) Analysis of Rad3 and Chk1 protein kinases defines different checkpoint responses. EMBO J. 17, 7239-7249
57. Matsuoka, S., Ballif, B.A., Smogorzewska, A., McDonald, 3rd, E.R., Hurov, K.E., Luo, J., Bakalarski, C.E., Zhao, Z., Solimini, N., Lerenthal, Y. et al. (2007) ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 316, 1160-1166
58. Meister, P., Taddei, A., Vernis, L., Poidevin, M., Gasser, S.M. and Baldacci, G. (2005) Temporal separation of replication and recombination requires the intra-S checkpoint. J. Cell. Biol. 168, 537-544
59. Michael, W.M., Ott, R., Fanning, E. and Newport, J. (2000) Activation of the DNA replication checkpoint through RNA synthesis by primase. Science 289, 2133-2137
60. Morin, I., Ngo, H.P., Greenall, A., Zubko, M.K., Morrice, N. and Lydall, D. (2008) Checkpoint-dependent phosphorylation of Exo1 modulates the DNA damage response. EMBO J. 27, 2400-2410
61. Morrison, A.J., Kim, J.A., Person, M.D., Highland, J., Xiao, J., Wehr, T.S., Hensley, S., Bao, Y., Shen, J., Collins, S.R. et al. (2007) Mec1/Tel1 phosphorylation of the INO80 chromatin remodeling complex influences DNA damage checkpoint responses. Cell 130, 499-511
62. Myung, K. and Kolodner, R.D. (2002) Suppression of genome instability by redundant S-phase checkpoint pathways in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. U.S.A. 99, 4500-4507
63. Myung, K., Datta, A. and Kolodner, R.D. (2001) Suppression of spontaneous chromosomal rearrangements by S phase checkpoint functions in Saccharomyces cerevisiae. Cell 104, 397-408
64. Nedelcheva, M.N., Roguev, A., Dolapchiev, L.B., Shevchenko, A., Taskov, H.B., Shevchenko, A., Stewart, A.F. and Stoynov, S.S. (2005) Uncoupling of unwinding from DNA synthesis implies regulation of MCM helicase by Tof1/Mrc1/Csm3 checkpoint complex. J. Mol. Biol. 347, 509-521
65. Noguchi, E., Noguchi, C., Du, L.L. and Russell, P. (2003) Swi1 prevents replication fork collapse and controls checkpoint kinase Cds1. Mol. Cell. Biol. 23, 7861-7874
66. Noguchi, E., Noguchi, C., McDonald, W.H., Yates, J.R., 3rd and Russell, P. (2004) Swi1 and Swi3 are components of a replication fork protection complex in fission yeast. Mol. Cell. Biol. 24, 8342-8355
67. Nyberg, K.A., Michelson, R.J., Putnam, C.W. and Weinert, T.A. (2002) Toward maintaining the genome: DNA damage and replication checkpoints. Annu. Rev. Genet. 36, 617-656
68. Osborn, A.J., Elledge, S.J. and Zou, L. (2002) Checking on the fork: the DNA-replication stress-response pathway. Trends Cell. Biol. 12, 509-516
69. Paciotti, V., Clerici, M., Scotti, M., Lucchini, G. and Longhese, M.P. (2001) Characterization of mec1 kinase-deficient mutants and of new hypomorphic mec1 alleles impairing subsets of the DNA damage response pathway. Mol. Cell. Biol. 21, 3913-3925
70. Papamichos-Chronakis, M. and Peterson, C.L. (2008) The Ino80 chromatin-remodeling enzyme regulates replisome function and stability. Nat. Struct. Mol. Biol. 15, 338-345
71. Paulovich, A.G. and Hartwell, L.H. (1995) A checkpoint regulates the rate of progression through S phase in S. cerevisiae in response to DNA damage. Cell 82, 841-847
72. Paulsen, R.D. and Cimprich, K.A. (2007) The ATR pathway: fine-tuning the fork. DNA Repair (Amsterdam) 6, 953-966
73. Pellicioli, A., Lucca, C., Liberi, G., Marini, F., Lopes, M., Plevani, P., Romano, A., Di Fiore, P.P. and Foiani, M. (1999) Activation of Rad53 kinase in response to DNA damage and its effect in modulating phosphorylation of the lagging strand DNA polymerase. EMBO J. 18, 6561-6572
74. Petermann, E., Maya-Mendoza, A., Zachos, G., Gillespie, D.A., Jackson, D.A. and Caldecott, K.W. (2006) Chk1 requirement for high global rates of replication fork progression during normal vertebrate S phase. Mol. Cell. Biol. 26, 3319-3326
75. Raveendranathan, M., Chattopadhyay, S., Bolon, Y.T., Haworth, J., Clarke, D.J. and Bielinsky, A.K. (2006) Genome-wide replication profiles of S-phase checkpoint mutants reveal fragile sites in yeast. EMBO J. 25, 3627-3639
76. Roberts, T.M., Kobor, M.S., Bastin-Shanower, S.A., Ii, M., Horte, S.A., Gin, J.W., Emili, A., Rine, J., Brill, S.J. and Brown, G.W. (2006) Slx4 regulates DNA damage checkpoint-dependent phosphorylation of the BRCT domain protein Rtt107/Esc4. Mol. Biol. Cell 17, 539-548
77. Roberts, T.M, Zaidi, I.W., Vaisica, J.A., Peter, M. and Brown, G.W. (2008) Regulation of Rtt107 recruitment to stalled DNA replication forks by the cullin Rtt101 and the Rtt109 acetyltransferase. Mol. Biol. Cell 19, 171-180.
78. Rouse, J. (2004) Esc4p, a new target of Mec1p (ATR), promotes resumption of DNA synthesis after DNA damage. EMBO J. 23, 1188-1197
79. Sanchez, Y., Bachant, J., Wang, H., Hu, F., Liu, D., Tetzlaff, M. and Elledge, S.J. (1999) Control of the DNA damage checkpoint by chk1 and rad53 protein kinases through distinct mechanisms. Science 286, 1166-1171
80. Santocanale, C. and Diffley, J.F.X. (1998) A Mec1- and Rad53-dependent checkpoint controls late-firing origins of DNA replication. Nature 395, 615-618
81. Santocanale, C., Sharma, K. and Diffley, J.F.X. (1999) Activation of dormant origins of DNA replication in budding yeast. Genes Dev. 13, 2360-2364
82. Segurado, M. and Diffley, J.F. (2008) Separate roles for the DNA damage checkpoint protein kinases in stabilizing DNA replication forks. Genes Dev. 22, 1816-1827
83. Shi, Y., Dodson, G.E., Mukhopadhyay, P.S., Shanware, N.P., Trinh, A.T. and Tibbetts, R.S. (2007) Identification of carboxyl-terminal MCM3 phosphorylation sites using polyreactive phosphospecific antibodies. J. Biol. Chem. 282, 9236-9243
84. Shimada, K., Oma, Y., Schleker, T., Kugou, K., Ohta, K., Harata, M. and Gasser, S.M. (2008) Ino80 chromatin remodeling complex promotes recovery of stalled replication forks. Curr. Biol. 18, 566-575
85. Shirahige, K., Hori, Y., Shiraishi, K., Yamashita, M., Takahashi, K., Obuse, C., Tsurimoto, T. and Yoshikawa, H. (1998) Regulation of DNA-replication origins during cell-cycle progression. Nature 395, 618-621
86. Smolka, M.B., Albuquerque, C.P., Chen, S.H. and Zhou, H. (2007) Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases. Proc. Natl. Acad. Sci. U.S.A. 104, 10364-10369
87. Sogo, J.M., Lopes, M. and Foiani, M. (2002) Fork reversal and ssDNA accumulation at stalled replication forks owing to checkpoint defects. Science 297, 599-602
88. Stokes, M.P., Van Hatten, R., Lindsay, H.D. and Michael, W.M. (2002) DNA replication is required for the checkpoint response to damaged DNA in Xenopus egg extracts. J. Cell. Biol. 158, 863-872
89. Szyjka, S.J., Aparicio, J.G., Viggiani, C.J., Knott, S., Xu, W., Tavare, S. and Aparicio, O.M. (2008) Rad53 regulates replication fork restart after DNA damage in Saccharomyces cerevisiae. Genes Dev. 22, 1906-1920
90. -/- mice. Genes Dev. 14, 1439-1447
91. Tercero, J.A., Labib, K. and Diffley, J.F. (2000) DNA synthesis at individual replication forks requires the essential initiation factor Cdc45p. EMBO J. 19, 2082-2093
92. Tercero, J.A. and Diffley, J.F. (2001) Regulation of DNA replication fork progression through damaged DNA by the Mec1/Rad53 checkpoint. Nature 412, 553-557
93. Tercero, J.A., Longhese, M.P. and Diffley, J.F. (2003) A central role for DNA replication forks in checkpoint activation and response. Mol. Cell 11, 1323-1336
94. Thaminy, S., Newcomb, B., Kim, J., Gatbonton, T., Foss, E., Simon, J. and Bedalov, A. (2007) Hst3 is regulated by Mec1-dependent proteolysis and controls the S phase checkpoint and sister chromatid cohesion by deacetylating histone H3 at lysine 56. J. Biol. Chem. 282, 37805-37814.
95. Tourriere, H. and Pasero, P. (2007) Maintenance of fork integrity at damaged DNA and natural pause sites. DNA Repair (Amsterdam) 6, 900-913
96. Tourriere, H., Versini, G., Cordon-Preciado, V., Alabert, C. and Pasero, P. (2005) Mrc1 and Tof1 promote replication fork progression and recovery independently of Rad53. Mol. Cell 19, 699-706
97. Trenz, K., Smith, E., Smith, S. and Costanzo, V. (2006) ATM and ATR promote Mre11 dependent restart of collapsed replication forks and prevent accumulation of DNA breaks. EMBO J. 25, 1764-1774
98. Trenz, K., Errico, A. and Costanzo, V. (2008) Plx1 is required for chromosomal DNA replication under stressful conditions. EMBO J. 27, 876-885
99. Vazquez, M.V., Rojas, V. and Tercero, J.A. (2008) Multiple pathways cooperate to facilitate DNA replication fork progression through alkylated DNA. DNA Repair (Amsterdam) 7, 1693-1704
100. Yoo, H.Y., Shevchenko, A., Shevchenko, A. and Dunphy, W.G. (2004) Mcm2 is a direct substrate of ATM and ATR during DNA damage and DNA replication checkpoint responses. J. Biol. Chem. 279, 53353-53364
101. You, Z., Harvey, K., Kong, L. and Newport, J. (2002) Xic1 degradation in Xenopus egg extracts is coupled to initiation of DNA replication. Genes Dev. 16, 1182-1194
102. Zachos, G., Rainey, M.D. and Gillespie, D.A. (2003) Chk1-deficient tumour cells are viable but exhibit multiple checkpoint and survival defects. EMBO J. 22, 713-723
103. Zachos, G., Rainey, M.D. and Gillespie, D.A. (2005) Chk1-dependent S-M checkpoint delay in vertebrate cells is linked to maintenance of viable replication structures. Mol. Cell. Biol. 25, 563-574
104. Zeng, Y., Forbes, K.C., Wu, Z., Moreno, S., Piwnica-Worms, H. and Enoch, T. (1998) Replication checkpoint requires phosphorylation of the phosphatase Cdc25 by Cds1 or Chk1. Nature 395, 507-510
105. Zhao, X., Muller, E.G. and Rothstein, R. (1998) A suppressor of two essential checkpoint genes identifies a novel protein that negatively affects dNTP pools. Mol. Cell 2, 329-340
106. Zhou, B.B. and Elledge, S.J. (2000) The DNA damage response: putting checkpoints in perspective. Nature 408, 433-439
107. Zou, L. and Elledge, S.J. (2003) Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 300, 1542-1548
108. Zou, L., Liu, D. and Elledge, S.J. (2003) Replication protein A-mediated recruitment and activation of Rad17 complexes. Proc. Natl. Acad. Sci. U.S.A. 100, 13827-13832
109. Zubko, M.K., Guillard, S. and Lydall, D. (2004) Exo1 and Rad24 differentially regulate generation of ssDNA at telomeres of Saccharomyces cerevisiae cdc13-1 mutants. Genetics 168, 103-115