Recombinational repair and restart of damaged replication forks

Nature Reviews Molecular Cell Biology

Volumn 3, Issue 11, 2002, Pages 859-870

  McGlynn, Peter ^a   Lloyd, Robert G ^a  

^a UNIVERSITY OF NOTTINGHAM   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

DNA POLYMERASE; DNA PRIMASE; ENDONUCLEASE; GENOMIC DNA; HELICASE; RECA PROTEIN;

COMPLEX FORMATION; DNA METABOLISM; DNA REPAIR; DNA REPLICATION; DNA TEMPLATE; ESCHERICHIA COLI; EUKARYOTE; GENE DUPLICATION; GENETIC RECOMBINATION; NONHUMAN; PRIORITY JOURNAL; PROKARYOTE; PROTEIN FUNCTION; REACTION ANALYSIS; REVIEW; YEAST;

DNA DAMAGE; DNA REPAIR; DNA REPLICATION; EUKARYOTIC CELLS; HUMANS; PROKARYOTIC CELLS; RECOMBINATION, GENETIC;

ESCHERICHIA COLI; EUKARYOTA; PROKARYOTA;

EID: 0036844340     PISSN: 14710072     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrm951     Document Type: Review

References (121)

1. Karow, J. K., Wu, L. & Hickson, I. D. RecQ family helicases: Roles in cancer and aging. Curr. Opin. Genet. Dev. 10, 32-38 (2000).
2. Venkitaraman, A. R. Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell 108, 171-182 (2002).
3. Maisnier-Patin, S., Nordstrom, K. & Dasgupta, S. Replication arrests during a single round of replication of the Escherichia coli chromosome in the absence of DnaC activity. Mol. Microbiol. 42, 1371-1382 (2001). The first direct measurement of the frequency with which replication forks stall In E. coil.
4. Cox, M. M. et al. The importance of repairing stalled replication forks. Nature 404, 37-41 (2000).
5. Kreuzer, K. N. Recombination-dependent DNA replication in phage T4. Trends Biochem. Sci. 25, 165-173 (2000).
6. Kogoma, T. Stable DNA replication: Interplay between DNA replication, homologous recombination, and transcription. Microbiol. Mol. Biol. Rev. 61, 212-238 (1997).
7. Paques, F. & Haber, J. E. Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rev. 63, 349-404 (1999).
8. Lindahl, T. & Wood, R. D. Quality control by DNA repair. Science 286, 1897-1905 (1999).
9. Kuzminov, A. Collapse and repair of replication forks in Escherichia coli. Mol. Microbiol. 16, 373-384 (1995).
10. McGlynn, R & Uoyd, R. G. Modulation of RNA polymerase by (p)ppGpp reveals a RecG-dependent mechanism for replication fork progression. Cell 101, 35-45 (2000). Identification of RecG as a helicase that generates Holliday junctions from damaged replication forks to assist fork progression.
11. Liu, B. & Alberts, B. M. Head-on collision between a DNA replication apparatus and RNA polymerase transcription complex. Science 267, 1131-1137 (1995).
12. Vilette, D., Ehrlich, S. D. & Michel, B. Transcription-induced deletions in Escherichia coli plasmids. Mol. Microbiol. 17, 493-504 (1995).
13. Krasilnikova, M. M., Samadashwily, G. M., Kraslinikov, A. S. & Mirkin, S. M. Transcription through a simple DNA repeat blocks replication elongation. EMBO J. 17, 5095-5102 (1998).
14. Chavez, S. et al. A protein complex containing Tho2, Hprl, Mft1 and a novel protein, Thp2, connects transcription elongation with mitotic recombination in Saccharomyces cerevisiae. EMBO J. 19, 5824-5834 (2000).
15. Brewer, B. J. When polymerases collide: Replication and the transcriptional organization of the E. coli chromosome. Cell 53, 679-686(1988).
16. Park, J. S., Marr, M. T. & Roberts, J. W. E. coli transcription repair coupling factor (mfd protein) rescues arrested complexes by promoting forward translocation. Cell 109, 757-767 (2002).
17. Fan, Q., Xu, F. & Petes,T. D. Meiosis-specific double-strand DNA breaks at the HIS4 recombination hot spot in the yeast Saccharomyces cerevisiae: Control in cis and trans. Mol. Cell. Biol. 15, 1679-1688 (1995).
18. Usdin, K. & Woodford, K. J. CGG repeats associated with DNA instability and chromosome fragility form structures that block DNA synthesis in vitro. Nucleic Acids Res. 23, 4202-4209 (1995).
19. Samadashwily, G. M., Raca, G. & Mirkin, S. M. Trinucleotide repeats affect DNA replication in vivo. Nature Genet. 17, 298-304 (1997).
20. Meneghini, R. & Hanawalt, R T4-endonudease V-sensitive sites in DNA from ultraviolet-irradiated human cells. Biochim. Biophys. Acta 425, 428-437 (1976).
21. Rupp, W. D., Wilde, C. E., Reno, D. L. & Howard-Flanders, P. Exchanges between DNA strands in ultraviolet-irradiated Escherichia coli. J. Mol. Biol. 61, 25-44 (1971). Identification of exchanges between sister duplexes after replication of DNA In cells exposed to UV light, which indicates that single-stranded gaps left in the replicated DNA at UV-induced pyrimidine dimers might be repaired by recombination with the Intact sister duplex.
22. West, S. C., Cassuto, E. & Howard-Flanders, P. Mechanism of E. coli RecA protein directed strand exchanges in post-replication repair of DNA. Nature 294, 659-662 (1981).
23. Gottesman, M. M., Hicks, M. L. & Gellert, M. Genetics and function of DNA ligase in Escherichia coli. J. Mol. Biol. 77, 531-547 (1973).
24. Johnston, L. H. & Nasmyth, K. A. Saccharomyces cerevisiae cell cycle mutant cdc9 is defective in DNA ligase. Nature 274, 891-893 (1978).
25. Svoboda, D. L. & Vos, J. M. Differential replication of a single, UV-induced lesion in the leading or lagging strand by a human cell extract: Fork uncoupling or gap formation. Proc. Natl. Acad. Sci. USA 92, 11975-11979 (1995).
26. Cordeiro-Stone, M., Makhov, A. M., Zaritskaya, L. S. & Griffith, J. D. Analysis of DNA replication forks encountering a pyrimidine dimer in the template to the leading strand. J. Mol. Biol. 289, 1207-1218 (1999).
27. Gruber, M., Wellinger, R. E. & Sogo, J. M. Architecture of the replication fork stalled at the 3′ end of yeast ribosomal genes. Mol. Cell. Biol. 20, 5777-5787 (2000).
28. Hill, T. M. & Marians, K. J. Escherichia coli Tus protein acts to arrest the progression of DNA replication forks in vitro. Proc. NatlAcad. Sci. USA 87, 2481-2485 (1990). References 25-28 provide the only descriptions of the structures of stalled replication forks.
29. Yancey-Wrona, J. E. & Matson, S. W. Bound Lac repressor protein differentially inhibits the unwinding reactions catalyzed by DNA helicases. Nucleic Acids Res. 20, 6713-6721 (1992).
30. Lane, H. E. & Denhardt, D. T. The rep mutation. IV Slower movement of replication forks in Escherichia coli rep strains. J. Mol. Biol. 97, 99-112 (1975).
31. Ivessa, A. S., Zhou, J. Q. & Zakian, V. A. The Saccharomyces Pif1p DNA helicase and the highly related Rrm3p have opposite effects on replication fork progression in ribosomal DNA. Cell 100, 479-489 (2000).
32. Bozhenok, L., Wade, P. A. & Varga-Weisz, P. WSTF-ISWI chromatin remodeling complex targets heterochromatic replication foci. EMBO J. 21, 2231-2241 (2002).
33. Marians, K. J., Hiasa, H., Kim, D. R. & McHenry, C. S. Role of the core DNA polymerase III subunits at the replication fork. α is the only subunit required for processive replication. J. Biol. Chem. 273, 2452-2457 (1998).
34. Tornaletti, S. & Hanawalt, P. C. Effect of DNA lesions on transcription elongation. Biochimie 81, 139-146 (1999).
35. Selby, C. P., Drapkin, R., Reinberg, D. & Sancar, A. RNA polymerase 11 stalled at a thymine dimer: Footprint and effect on excision repair. Nucleic Acids Res. 25, 787-793 (1997).
36. Pham, P., Bertram, J. G., O'Donnell, M., Woodgate, R. & Goodman, M. F. A model for SOS-lesion-targeted mutations in Escherichia coli. Nature 409, 366-370 (2001).
37. Goodman, M. F. & Tippin, B. The expanding polymerase universe. Nature Rev. Mol. Cell. Biol. 1, 101-109 (2000).
38. Tissier, A., McDonald, J. P., Frank, E. G. & Woodgate, R. polt, a remarkably error-prone human DNA polymerase. Genes Dev. 14, 1642-1650 (2000).
39. Baynton, I. & Fuchs, R. P. Lesions in DNA: Hurdles for polymerases. Trends Biochem. Sci. 25, 74-79 (2000).
40. Higgins, N. P., Kato, K. & Strauss, B. A model for replication repair in mammalian cells. J. Mol. Biol. 101, 417-425 (1976). The proposal of template switching as a mechanism of replication restart.
41. Viguera, E., Hernandez, P., Krimer. D. B., Lurz, R. & Schvartzman, J. B. Visualisation of plasmid replication intermediates containing reversed forks. Nucleic Acids Res. 28, 498-503 (2000).
42. Sogo, J. M., Lopez, M. & Foiani, M. Fork reversal and ssDNA accumulation at stalled replication forks owing to checkpoint defects. Science 297, 599-602 (2002). The direct observation of Holliday junctions and regions of ssDNA at replication forks In checkpoint-deficient yeast mutants.
43. Bidnenko, V., Ehrlich, S. D. & Michel, B. Replication fork collapse at replication terminator sequences. EMBO J. 21, 38983907 (2002).
44. Seigneur, M., Bidnenko, V., Ehrilch, S. D. & Michel, B. RuvAB acts at arrested replication forks. Cell 95, 419-430 (1998). A key study, which shows that damaged replication forks form Holliday junctions in vivo.
45. Rores, M. J., Bieme, H., Ehrlich, S. D. & Michel, B. Impairment of lagging strand synthesis triggers the formation of a RuvABC substrate at replication forks. EMBO J. 20, 619-629 (2001).
46. Zerbib, D., Mézard, C., George, H. & West, S. C. Coordinated actions of RuvABC in Holliday junction processing. J. Mol. Biol. 281, 621-630 (1998).
47. McGlynn, P. & Lloyd, R. G. Rescue of stalled replication forks by RecG: Simultaneous translocation on the leading and lagging strand templates supports an active DNA unwinding model of fork reversal and Holliday junction formation. Proc. Natl. Acad. Sci. USA 98, 8227-8234 (2001).
48. Gregg, A. V., McGlynn, P., Jaktaji, R. P. & Lloyd, R. G. Direct rescue of stalled DNA replication forks via the combined action of PriA and RecG helicase activities. Mol. Cell 9. 241-251 (2002).
49. Liu, J., Xu, L., Sandler, S. J. & Marians, K. J. Replication fork assembly at recombination intermediates is required for bacterial growth. Proc. Natl. Acad. Sci. USA 96, 3552-3555 (1999).
50. Cromie, G. A. & Leach. D. R. Control of crossing over. Mol. Cell 6, 815-826 (2000). The realization that the orientation of the cleavage of Holliday junctions by RuvABC is not random and that the actions of RuvABC at damaged replication forks (and other forms of DNA repair) might be biased against crossover formation, therefore avoiding chromosome segregation problems.
51. Michel, B., Recchia, G. D., Penel-Colin, M., Ehrlich, S. D. & Sherratt, D. J. Resolution of Holliday junctions by RuvABC prevents dimer formation in rep mutants and UV-irradiated cells. Mol. Microbiol. 37, 180-191 (2000).
52. Zou, H. & Rothstein, R. Holliday junctions accumulate in replication mutants via a RecA homolog-independent mechanism. Cell 90, 87-96 (1997).
53. Defossez, P. A. et al. Bimination of replication block protein Fob1 extends the life span of yeast mother cells. Mol. Cell 3, 447-455 (1999).
54. Sinclair, D. A. & Guarente, L. Extrachromosomal rDNA circles - A cause of aging in yeast. Cell 91, 1033-1042 (1997).
55. Cha, R. S. & Kleckner, N. ATR homolog Mecl promotes fork progression, thus averting breaks in replication slow zones. Science 297, 602-606 (2002). The correlation of chromosome breakage with stalling of the replication forks in slowly replicating zones of checkpoint-deficient yeast mutants indicates that checkpoint proteins might aid in the maintenance of normal replication fork progression.
56. Constantinou, A., Davies, A. A. & West, S. C. Branch migration and Holliday junction resolution catalyzed by activities from mammalian cells. Cell 104, 259-268 (2001).
57. Holmes, A. M. & Haber, J. E. Double-strand break repair in yeast requires both leading and lagging strand DNA polymerases. Cell 96, 415-424 (1999).
58. Malkova, A. et al. RAD51-independent break-induced replication to repair a broken chromosome depends on a distant enhancer site. Genes Dev. 15, 1055-1060 (2001).
59. Boddy, M. N. et al. Mus81-Eme1 are essential components of a Holliday junction resolvase. Cell. 107, 537 -548 (2001).
60. Chen, X. B. et al. Human Mus81-associated endonuclease cleaves Holliday junctions in vitro. Mol. Cell 8, 1117-1127 (2001).
61. Kaliraman, V., Mullen, J. R., Fricke, W. M., Bastin-Shanower, S. A. & Brill, S. J. Functional overlap between Sgsl-Top3 and the Mms4-Mus81 endonuclease. Genes Dev. 15, 2730-2740 (2001).
62. Doe, C. L.,Ahn,J. S., Dixon, J. & Whitby, M. C. Mus81-Eme1 and Rqhl involvement in processing stalled and collapsed replication forks. J. Biol. Chem. 277, 32753-32759 (2002). References 59-62 identified the Mus81 complex as a branched-DNA-specific endonuclease with a role in the repair of replication forks.
63. Boddy, M. N. et al. Damage tolerance protein Mus81 associates with the FHA1 domain of checkpoint kinase Cds1. Mol. Cell. Biol. 20, 8758-8766 (2000).
64. Johnson, M. E. et al. Positive selection of a gene family during the emergence of humans and African apes. Nature 413, 514-519 (2001).
65. Meneghini, R., Cordeiro-Stone, M. & Schumacher, R. I. Size and frequency of gaps in newly synthesized DNA of xeroderma pigmentosum human cells irradiated with ultraviolet light. Biophys. J. 33, 81-92 (1981).
66. McGlynn, P., Lloyd, R. G. & Marians, K. J. Formation of Hollidayjunctions by regression of nascent DNA in intermediates containing stalled replication forks: RecG stimulates regression even when the DNA is negatively supercoiled. Proc. Natl. Acad. Sci. USA 98, 8235-8240 (2001).
67. Singleton, M. R.,Scaife,S. & Wigley, D. B. Structural analysis of DNA replication fork reversal by RecG. Cell 107, 79-89 (2001). The structure of RecG revealed how a single polypeptide could unwind both the leading and the lagging strands, and promote reannealing of the parental strands, to allow Holliday junction formation at stalled replication forks.
68. Postow, L. et al. Positive torsional strain causes the formation of a four-way junction at replication forks. J. Biol. Biol. Chem. 276, 2790-2796 (2001).
69. Rangarajan, S., Woodgate, R. & Goodman, M. F. Replication restart in UV-irradiated Escherichia coli involving pols II, III, V, PriA, RecA and RecFOR proteins. Mol.. Microbiol. 43, 617-628 (2002).
70. Parsons, C. A., Tsaneva, I., Uoyd, R. G. & West, S. C. Interaction of Escherichia coli RuvA and RuvB proteins with synthetic Holliday junctions. Proc. Natl. Acad. Sci. USA 89, 5452-5456 (1992).
71. Lloyd, R. G. & Sharpies, G. J. Dissociation of synthetic Holliday junctions by E. coli RecG protein. EMBO J. 12, 17-22 (1993).
72. Bolt, E. L. & Lloyd, R. G. Substrate-specificity of RusA resolvase reveals the DNA structures targeted by RuvAB and RecG in vivo. Mol. Cell 10, 187-198 (2002).
73. Liu, L. F. & Wang, J. C. Supercoiling of the DNA template during transcription. Proc. Natl. Acad. Sci. USA 84, 7024-7027(1987).
74. Seigneur, M., Ehrlich, S. D. & Michel, B. RuvABC-dependent double-strand breaks in dnaBts mutants require recA. Mol. Microbiol. 38, 565-574 (2000).
75. Robu, M. E., Inman, R. B. & Cox, M. M. RecA protein promotes the regression of stalled replication forks in vitro. Proc. Natl. Acad. Sci. USA 98, 8211-8218 (2001).
76. McGlynn, P. & Lloyd, R. G. Action of RuvAB at replication fork structures. J. Biol. Chem. 276, 41938-41944 (2001).
77. Hanada, K. et al. RecQ DNA helicase is a suppressor of illegitimate recombination in Escherichia coli. Proc. Natl. Acad. Sci. USA 94, 3860-3865 (1997).
78. Harmon, F. G. & Kowalczykowski, S. C. RecQ helicase, in concert with RecA and SSB proteins, initiates and disrupts DNA recombination. Genes Dev. 12, 1134-1144 (1998).
79. Courcelle, J. & Hanawalt, P. C. RecQ and RecJ process blocked replication forks prior to the resumption of replication in UV-irradiated Escherichia coli. Mol. Gen. Genet. 262, 543-551 (1999).
80. Courcelle, J., Crowley, D. J. & Hanawalt, P. C. Recovery of DNA replication in UV-irradiated Escherichia coli requires both excision repair and recF protein function. J. Bacteriol. 181, 916-922 (1999).
81. Sharples, G.J., Ingleston, S. M. & Lloyd, R. G. Holliday junction processing in bacteria: Insights from the evolutionary conservation of RuvABC, RecG, and RusA. J. Bacteriol. 181, 5543-5550 (1999).
82. Aboussekhra, A., Chanet, R., Adjiri, A. & Fabre, F. Semidominant suppressors of Srs2 helicase mutations of Saccharomyces cerevisiae map in the RAD51 gene, whose sequence predicts a protein with similarities to procaryotic RecA proteins. Mol. Cell. Biol. 12, 3224-3234 (1992).
83. Karow, J. K., Constantinou, A., Li, J. L., West, S. C. & Hickson, I. D. The Bloom's syndrome gene product promotes branch migration of Holliday junctions. Proc. Natl. Acad. Sci. USA 97, 6504-6508 (2000).
84. Constantinou, A. et al. Wemer's syndrome protein (WRN)(VVRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest. EMBO Rep. 1, 80-84 (2000).
85. Mohaghegh, R, Karow, J. K., Brosh, R. M. Jr, Bohr, V. A. & Hickson, I. D. The Bloom's and Werner's syndrome proteins are DNA structure-specific helicases. Nucleic Acids Res. 29, 2843-2849(2001).
86. Yan, H., Chen, C. Y., Kobayashi, R. & Newport, J. Replication focus-forming activity 1 and the Werner syndrome gene product. Nature Genet. 19, 375-378 (1998).
87. Brosh, R. M. Jr. et al. Replication protein A physically interacts with the Bloom's syndrome protein and stimulates its helicase activity. J. Biol. Chem. 275, 23500-23508 (2000).
88. Murray, J. M., Lindsay, H. D., Munday, C. A. & Carr, A.M. Role of Schizosaccharomyces pombe RecQ homolog, recombination, and checkpoint genes in UV damage tolerance. Mol. Cell. Biol. 17, 6868-6875 (1997).
89. Doe, C. L., Dixon, J., Osman, F. & Whitby, M. C. Partial suppression of the fission yeast rqhl (-) phenotype by expression of a bacterial Holliday junction resolvase. EMBO J. 19, 2751-2762 (2000).
90. Bennett, R. J., Keck, J. L. & Wang, J. C. Binding specificity determines polarity of DNA unwinding by the Sgsl protein of S. cerevisiae. J. Mol. Biol. 289, 235-248 (1999).
91. Gangloff, S., McDonald, J. P., Bendixen, C,. Arthur, L. & Rothstein, R. The yeast type I topoisomerase Top3 interacts with Sgs1, a DNA helicase homolog: A potential eukaryotic reverse gyrase. Mol. Cell. Biol. 14, 83918398 (1994).
92. Harmon, F. G., DiGate, R. J. & Kowalczykowski, S. C. RecQ helicase and topoisomerase III comprise a novel DNA strand passage function: A conserved mechanism for control of DNA recombination. Mol. Cell 3, 611-820 (1999).
93. Wu, L. et al. The Bloom's syndrome gene product interacts with topoisomerase III. J. Biol. Chem. 275, 9636-9644 (2000).
94. Kato, J. & Katayama, T. Hda, a novel DnaA-related protein, regulates the replication cycle in Escherichia coli. EMBO J. 20, 4253-4262 (2001).
95. Nguyen, V. Q., Co, C. & Li, J. J. Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms. Nature 411, 1068-1073 (2001).
96. Nurse, P., Zavitz K. H. & Marians, K. J. Inactivation of the Escherichia coli priA DNA replication protein induces the SOS response. J. Bacteriol. 173, 6686-6693 (1991).
97. Kogoma, T., Cadwell, G. W., Barnard, K. G. & Asai, T. The DNA replication priming protein, PriA, is required for homologous recombination and double-strand break repair J. Bacteriol. 178, 1258-1264 (1996). References 96 and 97 showed the crucial links between replication and recombination, and the central role of PriA.
98. Jones, J. M. & Nakai, H. Duplex opening by primosome protein PriA for replisome assembly on a recombination intermediate. J. Mol. Biol. 289, 503-516 (1999).
99. Nurse, P., Liu, J. & Marians, K. J. Two modes of PriA binding to DNA. J. Biol. Chem. 274, 25026-25032 (1999).
100. Jones, J. M. & Nakai, H. Escherichia coli PriA helicase: Fork binding orients the helicase to unwind the lagging strand side of arrested replication forks. J. Mol. Biol. 312, 935-947 (2001).
101. Zavitz, K. H. & Marians, K. J. ATPase-deficient mutants of the Escherichia coli DNA replication protein PriA are capable of catalyzing the assembly of active primosomes. J. Biol. Chem. 267, 6933-6940 (1992).
102. Sandler, S. J., Samra, H. S. & Clark, A. J. Differential suppression of priA2::kan phenotypes in Escherichia coli K-12 by mutations in priA, lexA, and dnaC. Genetics 143, 5-13 (1996).
103. Sandler, S. J. Multiple genetic pathways for restarting DNA replication forks in Escherichia coli K-12. Genetics 155, 487-497 (2000).
104. Baur, J. A., Zou, Y., Shay, J. W. & Wright, W. E. Telomere position effect in human cells. Science 292, 2075-2077 (2001).
105. Lemon, K. R. & Grossman, A. D. Movement of replicating DNA through a stationary replisome. Mol. Cell 6, 1321-1330 (2000).
106. Cook, P. R. The organization of replication and transcription. Science 284, 1790-1795 (1999).
107. Lisby, M., Rothstein, R. & Mortensen, U. H. Rad52 forms DNA repair and recombination centers during S phase. Proc. Natl. Acad. Sci. USA 98, 8276-8282 (2001).
108. Essers, J. etal, Nuclear dynamics of RAD52 group homologous recombination proteins in response to DNA damage. EMBO J. 21, 2030-2037 (2002).
109. Phair, R. D. & Misteli, T. High mobility of proteins in the mammalian cell nucleus. Nature 404, 604-609 (2000).
110. Courcelle, J., Khodursky, A., Peter, B., Brown, P. O. & Hanawalt, P. C. Comparative gene expression profiles following UV exposure in wild-type and SOS-deficient Escherichia coli. Genetics 158, 41-64 (2001).
111. Wagner, J. et al. The dinB gene encodes a novel E. coli DNA polymerase, DNA pol IV, involved in mutagenesis. Mol. Cell 4, 281-286 (1999).
112. Zhou, B. B. & Elledge, S. J. The DNA damage response: Putting checkpoints in perspective. Nature 408, 433-439 (2000).
113. Caspari, T. & Carr, A. M. Checkpoints: How to flag up double-strand breaks. Curr. Biol. 12, R105-R107 (2002).
114. Tercero, J. A. & Diffley, J. F. Regulation of DNA replication fork progression through damaged DNA by the Mec1/Rad53 checkpoint. Nature 412, 553-557 (2001).
115. Lopes, M. et al. The DNA replication checkpoint response stabilizes stalled replication forks. Nature 412, 557-561 (2001). References 114 and 115 showed that the checkpoint response can stabilize stalled replication forks to prevent their collapse, facilitating the eventual completion of replication.
116. Brush, G. S., Morrow, D. M., Hieter, P. & Kelly, T. J. The ATM homologue MEC1 is required for phosphorylation of replication protein A in yeast. Proc. Natl. Acad. Sci. USA 93, 15075-15080 (1996).
117. Pellicioli, A. et al. 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 (1999).
118. Zhao, X. & Rothstein, R. The Dun1 checkpoint kinase phosphorylates and regulates the ribonucleotide reductase inhibitor Sml1. Proc. Natl. Acad. Sci. USA 99, 3746-3751 (2002).
119. Bashkirov, V. I., King, J. S., Bashkirova, E. V., Schmuckli-Maurer, J. & Heyer, W. D. DNA repair protein Rad55 is a terminal substrate of the DNA damage checkpoints. Mol. Cell. Biol. 20, 4393-4404 (2000).
120. Carr, A. M. Checking that replication breakdown is not terminal. Science 297, 557-558 (2002).
121. Aguilera, A. Double-strand break repair: Are Rad51/RecA-DNA joints barriers to DNA replication? Trends Genet. 17, 318-321 (2001).