Role of yeast Rad5 and its human orthologs, HLTF and SHPRH in DNA damage tolerance

DNA Repair

Volumn 9, Issue 3, 2010, Pages 257-267

  Unk, Ildiko ^a   Hajdú, Ildikó ^a   Blastyák, András ^a   Haracska, Lajos ^a  

^a INSTITUTE OF EXPERIMENTAL MEDICINE   (Hungary)

Author keywords

Damage bypass; DNA polymerase; DNA translocase; Replication; SWI SNF2; Ubiquitin

Indexed keywords

DNA; NUCLEIC ACID BINDING PROTEIN; PROTEIN RAD5; RAD18 PROTEIN; UBIQUITIN CONJUGATING ENZYME; UNCLASSIFIED DRUG;

DNA DAMAGE; DNA REPLICATION; DNA SYNTHESIS; EUKARYOTIC CELL; GENE STRUCTURE; GENETIC CONSERVATION; IN VIVO STUDY; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN FUNCTION; REVIEW;

ANIMALS; DNA DAMAGE; DNA HELICASES; DNA REPLICATION; DNA-BINDING PROTEINS; HUMANS; SACCHAROMYCES CEREVISIAE; SACCHAROMYCES CEREVISIAE PROTEINS; TRANSCRIPTION FACTORS; UBIQUITIN-PROTEIN LIGASES;

EUKARYOTA; SACCHAROMYCES CEREVISIAE;

EID: 77049127484     PISSN: 15687864     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.dnarep.2009.12.013     Document Type: Review

References (100)

1. Prakash S., Johnson R.E., and Prakash L. Eukaryotic translesion synthesis DNA polymerases: specificity of structure and function. Annu. Rev. Biochem. 74 (2005) 317-353
2. Rupp W.D., and Howard-Flanders P. Discontinuities in the DNA synthesized in an excision-defective strain of Escherichia coli following ultraviolet irradiation. J. Mol. Biol. 31 (1968) 291-304
3. Fujiwara Y., and Tatsumi M. Replicative bypass repair of ultraviolet damage to DNA of mammalian cells: caffeine sensitive and caffeine resistant mechanisms. Mutat. Res. 37 (1976) 91-110
4. Higgins N.P., Kato K., and Strauss B. A model for replication repair in mammalian cells. J. Mol. Biol. 101 (1976) 417-425
5. Hotchkiss R.D. Models of genetic recombination. Annu. Rev. Microbiol. 28 (1974) 445-468
6. Nilsen T., and Baglioni C. Unusual base-pairing of newly synthesized DNA in HeLa cells. J. Mol. Biol. 133 (1979) 319-338
7. Zannis-Hadjopoulos M., Persico M., and Martin R.G. The remarkable instability of replication loops provides a general method for the isolation of origins of DNA replication. Cell 27 (1981) 155-163
8. Cotta-Ramusino C., Fachinetti D., Lucca C., Doksani Y., Lopes M., Sogo J., and Foiani M. Exo1 processes stalled replication forks and counteracts fork reversal in checkpoint-defective cells. Mol. Cell 17 (2005) 153-159
9. Zhang H., and Lawrence C.W. The error-free component of the RAD6/RAD18 DNA damage tolerance pathway of budding yeast employs sister-strand recombination. Proc. Natl. Acad. Sci. U.S.A. 102 (2005) 15954-15959
10. Torres-Ramos C.A., Prakash S., and Prakash L. Requirement of RAD5 and MMS2 for postreplication repair of UV-damaged DNA in Saccharomyces cerevisiae. Mol. Cell Biol. 22 (2002) 2419-2426
11. Liefshitz B., Steinlauf R., Friedl A., Eckardt-Schupp F., and Kupiec M. Genetic interactions between mutants of the 'error-prone' repair group of Saccharomyces cerevisiae and their effect on recombination and mutagenesis. Mutat. Res. 407 (1998) 135-145
12. Branzei D., Vanoli F., and Foiani M. SUMOylation regulates Rad18-mediated template switch. Nature 456 (2008) 915-920
13. Blastyak A., Pinter L., Unk I., Prakash L., Prakash S., and Haracska L. Yeast Rad5 protein required for postreplication repair has a DNA helicase activity specific for replication fork regression. Mol. Cell 28 (2007) 167-175
14. Motegi A., Liaw H.J., Lee K.Y., Roest H.P., Maas A., Wu X., Moinova H., Markowitz S.D., Ding H., Hoeijmakers J.H., et al. Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks. Proc. Natl. Acad. Sci. U.S.A. 105 (2008) 12411-12416
15. Motegi A., Sood R., Moinova H., Markowitz S.D., Liu P.P., and Myung K. Human SHPRH suppresses genomic instability through proliferating cell nuclear antigen polyubiquitination. J. Cell Biol. 175 (2006) 703-708
16. Unk I., Hajdu I., Fatyol K., Hurwitz J., Yoon J.H., Prakash L., Prakash S., and Haracska L. Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination. Proc. Natl. Acad. Sci. U.S.A. 105 (2008) 3768-3773
17. Unk I., Hajdu I., Fatyol K., Szakal B., Blastyak A., Bermudez V., Hurwitz J., Prakash L., Prakash S., and Haracska L. Human SHPRH is a ubiquitin ligase for Mms2-Ubc13-dependent polyubiquitylation of proliferating cell nuclear antigen. Proc. Natl. Acad. Sci. U.S.A. 103 (2006) 18107-18112
18. Blastyak A., Hajdu I., Unk I., and Haracska L. Role of double-stranded DNA translocase activity of human HLTF in replication of damaged DNA. Mol. Cell Biol. (2009)
19. Prakash L. Characterization of postreplication repair in Saccharomyces cerevisiae and effects of rad6, rad18, rev3 and rad52 mutations. Mol. Gen. Genet. 184 (1981) 471-478
20. Lawrence C.W. Mutagenesis in Saccharomyces cerevisiae. Adv. Genet. 21 (1982) 173-254
21. Prakash S., Sung P., and Prakash L. DNA repair genes and proteins of Saccharomyces cerevisiae. Annu. Rev. Genet. 27 (1993) 33-70
22. Bailly V., Lamb J., Sung P., Prakash S., and Prakash L. Specific complex-formation between yeast Rad6 and Rad18 proteins-a potential mechanism for targeting Rad6 ubiquitin-conjugating activity to DNA-damage sites. Genes Dev. 8 (1994) 811-820
23. Bailly V., Lauder S., Prakash S., and Prakash L. Yeast DNA repair proteins Rad6 and Rad18 form a heterodimer that has ubiquitin conjugating, DNA binding, and ATP hydrolytic activities. J. Biol. Chem. 272 (1997) 23360-23365
24. Jentsch S., McGrath J.P., and Varshavsky A. The yeast DNA repair gene RAD6 encodes a ubiquitin-conjugating enzyme. Nature 329 (1987) 131-134
25. Hoege C., Pfander B., Moldovan G.L., Pyrowolakis G., and Jentsch S. RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO. Nature 419 (2002) 135-141
26. Haracska L., Unk I., Prakash L., and Prakash S. Ubiquitylation of yeast proliferating cell nuclear antigen and its implications for translesion DNA synthesis. Proc. Natl. Acad. Sci. U.S.A. 103 (2006) 6477-6482
27. Wood A., Garg P., and Burgers P.M. 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. J. Biol. Chem. 282 (2007) 20256-20263
28. Huttner D., and Ulrich H.D. Cooperation of replication protein A with the ubiquitin ligase Rad18 in DNA damage bypass. Cell Cycle 7 (2008) 3629-3633
29. Stelter P., and Ulrich H.D. Control of spontaneous and damage-induced mutagenesis by SUMO and ubiquitin conjugation. Nature 425 (2003) 188-191
30. Haracska L., Prakash S., and Prakash L. Yeast Rev1 protein is a G template-specific DNA polymerase. J. Biol. Chem. 277 (2002) 15546-15551
31. Haracska L., Unk I., Johnson R.E., Johansson E., Burgers P.M.J., Prakash S., and Prakash L. Roles of yeast DNA polymerases delta and zeta and of Rev1 in the bypass of abasic sites. Genes Dev. 15 (2001) 945-954
32. Nelson J.R., Lawrence C.W., and Hinkle D.C. Deoxycytidyl transferase activity of yeast REV1 protein. Nature 382 (1996) 729-731
33. Hashimoto K., Tominaga Y., Nakabeppu Y., and Moriya M. Futile short-patch DNA base excision repair of adenine:8-oxoguanine mispair. Nucleic Acids Res. 32 (2004) 5928-5934
34. Johnson R.E., Washington M.T., Haracska L., Prakash S., and Prakash L. Eukaryotic polymerases iota and zeta act sequentially to bypass DNA lesions. Nature 406 (2000) 1015-1019
35. Nelson J.R., Lawrence C.W., and Hinkle D.C. Thymine-thymine dimer bypass by yeast DNA polymerase zeta. Science 272 (1996) 1646-1649
36. Johnson R.E., Prakash S., and Prakash L. Efficient bypass of a thymine-thymine dimer by yeast DNA polymerase, Pol eta. Science 283 (1999) 1001-1004
37. McDonald J.P., Levine A.S., and Woodgate R. The Saccharomyces cerevisiae RAD30 gene, a homologue of Escherichia coli dinB and umuC, is DNA damage inducible and functions in a novel error-free postreplication repair mechanism. Genetics 147 (1997) 1557-1568
38. Yu S.L., Johnson R.E., Prakash S., and Prakash L. Requirement of DNA polymerase eta for error-free bypass of UV-induced CC and TC photoproducts. Mol. Cell Biol. 21 (2001) 185-188
39. Broomfield S., Chow B.L., and Xiao W. MMS2, encoding a ubiquitin-conjugating-enzyme-like protein, is a member of the yeast error-free postreplication repair pathway. Proc. Natl. Acad. Sci. U.S.A. 95 (1998) 5678-5683
40. Hofmann R.M., and Pickart C.M. Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair. Cell 96 (1999) 645-653
41. Johnson R.E., Henderson S.T., Petes T.D., Prakash S., Bankmann M., and Prakash L. Saccharomyces cerevisiae RAD5-encoded DNA repair protein contains DNA helicase and zinc-binding sequence motifs and affects the stability of simple repetitive sequences in the genome. Mol. Cell Biol. 12 (1992) 3807-3818
42. Brusky J., Zhu Y., and Xiao W. UBC13, a DNA-damage-inducible gene, is a member of the error-free postreplication repair pathway in Saccharomyces cerevisiae. Curr. Genet. 37 (2000) 168-174
43. Ulrich H.D., and Jentsch S. Two RING finger proteins mediate cooperation between ubiquitin-conjugating enzymes in DNA repair. EMBO J. 19 (2000) 3388-3397
44. Carlile C.M., Pickart C.M., Matunis M.J., and Cohen R.E. Synthesis of free and proliferating cell nuclear antigen-bound polyubiquitin chains by the RING E3 ubiquitin ligase Rad5. J. Biol. Chem. 284 (2009) 29326-29334
45. Parker J.L., and Ulrich H.D. Mechanistic analysis of PCNA poly-ubiquitylation by the ubiquitin protein ligases Rad18 and Rad5. EMBO J. 28 (2009) 3657-3666
46. Johnson R.E., Prakash S., and Prakash L. Yeast DNA repair protein RAD5 that promotes instability of simple repetitive sequences is a DNA-dependent ATPase. J. Biol. Chem. 269 (1994) 28259-28262
47. Iyer L.M., Babu M.M., and Aravind L. The HIRAN domain and recruitment of chromatin remodeling and repair activities to damaged DNA. Cell Cycle 5 (2006) 775-782
48. Gangavarapu V., Haracska L., Unk I., Johnson R.E., Prakash S., and Prakash L. Mms2-Ubc13-dependent and -independent roles of Rad5 ubiquitin ligase in postreplication repair and translesion DNA synthesis in Saccharomyces cerevisiae. Mol. Cell Biol. 26 (2006) 7783-7790
49. Kiakos K., Howard T.T., Lee M., Hartley J.A., and McHugh P.J. Saccharomyces cerevisiae RAD5 influences the excision repair of DNA minor groove adducts. J. Biol. Chem. 277 (2002) 44576-44581
50. Lawrence C.W., and Christensen R. UV mutagenesis in radiation-sensitive strains of yeast. Genetics 82 (1976) 207-232
51. Hishida T., Kubota Y., Carr A.M., and Iwasaki H. RAD6-RAD18-RAD5-pathway-dependent tolerance to chronic low-dose ultraviolet light. Nature 457 (2009) 612-615
52. Koken M.H., Reynolds P., Jaspers-Dekker I., Prakash L., Prakash S., Bootsma D., and Hoeijmakers J.H. Structural and functional conservation of two human homologs of the yeast DNA repair gene RAD6. Proc. Natl. Acad. Sci. U.S.A. 88 (1991) 8865-8869
53. Tateishi S., Sakuraba Y., Masuyama S., Inoue H., and Yamaizumi M. Dysfunction of human Rad18 results in defective postreplication repair and hypersensitivity to multiple mutagens. Proc. Natl. Acad. Sci. U.S.A. 97 (2000) 7927-7932
54. Chiu R.K., Brun J., Ramaekers C., Theys J., Weng L., Lambin P., Gray D.A., and Wouters B.G. Lysine 63-polyubiquitination guards against translesion synthesis-induced mutations. PLoS Genet. 2 (2006) e116
55. Watanabe K., Tateishi S., Kawasuji M., Tsurimoto T., Inoue H., and Yamaizumi M. Rad18 guides poleta to replication stalling sites through physical interaction and PCNA monoubiquitination. EMBO J. 23 (2004) 3886-3896
56. Moraes T.F., Edwards R.A., McKenna S., Pastushok L., Xiao W., Glover J.N., and Ellison M.J. Crystal structure of the human ubiquitin conjugating enzyme complex, hMms2-hUbc13. Nat. Struct. Biol. 8 (2001) 669-673
57. MacKay C., Toth R., and Rouse J. Biochemical characterisation of the SWI/SNF family member HLTF. Biochem. Biophys. Res. Commun. 390 (2009) 187-191
58. Chen I.P., Mannuss A., Orel N., Heitzeberg F., and Puchta H. A homolog of ScRAD5 is involved in DNA repair and homologous recombination in Arabidopsis. Plant Physiol. 146 (2008) 1786-1796
59. Doe C.L., Murray J.M., Shayeghi M., Hoskins M., Lehmann A.R., Carr A.M., and Watts F.Z. Cloning and characterisation of the Schizosaccharomyces pombe rad8 gene, a member of the SNF2 helicase family. Nucleic Acids Res. 21 (1993) 5964-5971
60. Gong X., Kaushal S., Ceccarelli E., Bogdanova N., Neville C., Nguyen T., Clark H., Khatib Z.A., Valentine M., Look A.T., et al. Developmental regulation of Zbu1, a DNA-binding member of the SWI2/SNF2 family. Dev. Biol. 183 (1997) 166-182
61. Malik M., and Nitiss J.L. DNA repair functions that control sensitivity to topoisomerase-targeting drugs. Eukaryot. Cell 3 (2004) 82-90
62. Zhang Q., Ekhterae D., and Kim K.H. Molecular cloning and characterization of P113, a mouse SNF2/SWI2-related transcription factor. Gene 202 (1997) 31-37
63. Eki T., Ishihara T., Katsura I., and Hanaoka F. A genome-wide survey and systematic RNAi-based characterization of helicase-like genes in Caenorhabditis elegans. DNA Res. 14 (2007) 183-199
64. Pothof J., van Haaften G., Thijssen K., Kamath R.S., Fraser A.G., Ahringer J., Plasterk R.H., and Tijsterman M. Identification of genes that protect the C. elegans genome against mutations by genome-wide RNAi. Genes Dev. 17 (2003) 443-448
65. Pena P.V., Davrazou F., Shi X., Walter K.L., Verkhusha V.V., Gozani O., Zhao R., and Kutateladze T.G. Molecular mechanism of histone H3K4me3 recognition by plant homeodomain of ING2. Nature 442 (2006) 100-103
66. Sheridan P.L., Schorpp M., Voz M.L., and Jones K.A. Cloning of an SNF2/SWI2-related protein that binds specifically to the SPH motifs of the SV40 enhancer and to the HIV-1 promoter. J. Biol. Chem. 270 (1995) 4575-4587
67. Ding H., Descheemaeker K., Marynen P., Nelles L., Carvalho T., Carmo-Fonseca M., Collen D., and Belayew A. Characterization of a helicase-like transcription factor involved in the expression of the human plasminogen activator inhibitor-1 gene. DNA Cell Biol. 15 (1996) 429-442
68. Mahajan M.C., and Weissman S.M. DNA-dependent adenosine triphosphatase (helicaselike transcription factor) activates beta-globin transcription in K562 cells. Blood 99 (2002) 348-356
69. Moinova H.R., Chen W.D., Shen L., Smiraglia D., Olechnowicz J., Ravi L., Kasturi L., Myeroff L., Plass C., Parsons R., et al. HLTF gene silencing in human colon cancer. Proc. Natl. Acad. Sci. U.S.A. 99 (2002) 4562-4567
70. Fukuoka T., Hibi K., and Nakao A. Aberrant methylation is frequently observed in advanced esophageal squamous cell carcinoma. Anticancer Res. 26 (2006) 3333-3335
71. Hibi K., Nakayama H., Kanyama Y., Kodera Y., Ito K., Akiyama S., and Nakao A. Methylation pattern of HLTF gene in digestive tract cancers. Int. J. Cancer 104 (2003) 433-436
72. Leung W.K., Yu J., Bai A.H., Chan M.W., Chan K.K., To K.F., Chan F.K., Ng E.K., Chung S.C., and Sung J.J. Inactivation of helicase-like transcription factor by promoter hypermethylation in human gastric cancer. Mol. Carcinog. 37 (2003) 91-97
73. Oue N., Mitani Y., Motoshita J., Matsumura S., Yoshida K., Kuniyasu H., Nakayama H., and Yasui W. Accumulation of DNA methylation is associated with tumor stage in gastric cancer. Cancer 106 (2006) 1250-1259
74. Capouillez A., Debauve G., Decaestecker C., Filleul O., Chevalier D., Mortuaire G., Coppee F., Leroy X., Belayew A., and Saussez S. The helicase-like transcription factor is a strong predictor of recurrence in hypopharyngeal but not in laryngeal squamous cell carcinomas. Histopathology 55 (2009) 77-90
75. Capouillez A., Decaestecker C., Filleul O., Chevalier D., Coppee F., Leroy X., Belayew A., and Saussez S. Helicase-like transcription factor exhibits increased expression and altered intracellular distribution during tumor progression in hypopharyngeal and laryngeal squamous cell carcinomas. Virchows Arch. 453 (2008) 491-499
76. Lee J.H., Kavanagh J.J., Wildrick D.M., Wharton J.T., and Blick M. Frequent loss of heterozygosity on chromosomes 6q, 11, and 17 in human ovarian carcinomas. Cancer Res. 50 (1990) 2724-2728
77. Mazurenko N., Attaleb M., Gritsko T., Semjonova L., Pavlova L., Sakharova O., and Kisseljov F. High resolution mapping of chromosome 6 deletions in cervical cancer. Oncol. Rep. 6 (1999) 859-863
78. Millikin D., Meese E., Vogelstein B., Witkowski C., and Trent J. Loss of heterozygosity for loci on the long arm of chromosome 6 in human malignant melanoma. Cancer Res. 51 (1991) 5449-5453
79. Trent J.M., Stanbridge E.J., McBride H.L., Meese E.U., Casey G., Araujo D.E., Witkowski C.M., and Nagle R.B. Tumorigenicity in human melanoma cell lines controlled by introduction of human chromosome 6. Science 247 (1990) 568-571
80. Sood R., Makalowska I., Galdzicki M., Hu P., Eddings E., Robbins C.M., Moses T., Namkoong J., Chen S., and Trent J.M. Cloning and characterization of a novel gene, SHPRH, encoding a conserved putative protein with SNF2/helicase and PHD-finger domains from the 6q24 region. Genomics 82 (2003) 153-161
81. Cordeiro-Stone M., Zaritskaya L.S., Price L.K., and Kaufmann W.K. Replication fork bypass of a pyrimidine dimer blocking leading strand DNA synthesis. J. Biol. Chem. 272 (1997) 13945-13954
82. Pages V., and Fuchs R.P. Uncoupling of leading- and lagging-strand DNA replication during lesion bypass in vivo. Science 300 (2003) 1300-1303
83. Svoboda D.L., and 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. U.S.A. 92 (1995) 11975-11979
84. Lehmann A.R., and Fuchs R.P. Gaps and forks in DNA replication: rediscovering old models. DNA Repair (Amst) 5 (2006) 1495-1498
85. Lopes M., Foiani M., and Sogo J.M. Multiple mechanisms control chromosome integrity after replication fork uncoupling and restart at irreparable UV lesions. Mol. Cell 21 (2006) 15-27
86. Durr H., Flaus A., Owen-Hughes T., and Hopfner K.P. Snf2 family ATPases and DExx box helicases: differences and unifying concepts from high-resolution crystal structures. Nucleic Acids Res. 34 (2006) 4160-4167
87. Flaus A., Martin D.M., Barton G.J., and Owen-Hughes T. Identification of multiple distinct Snf2 subfamilies with conserved structural motifs. Nucleic Acids Res. 34 (2006) 2887-2905
88. Heyer W.D., Li X., Rolfsmeier M., and Zhang X.P. Rad54: the Swiss Army knife of homologous recombination?. Nucleic Acids Res. 34 (2006) 4115-4125
89. Gangavarapu V., Prakash S., and Prakash L. Requirement of RAD52 group genes for postreplication repair of UV-damaged DNA in Saccharomyces cerevisiae. Mol. Cell Biol. 27 (2007) 7758-7764
90. Lebofsky R., Heilig R., Sonnleitner M., Weissenbach J., and Bensimon A. DNA replication origin interference increases the spacing between initiation events in human cells. Mol. Biol. Cell 17 (2006) 5337-5345
91. Smith S., Hwang J.Y., Banerjee S., Majeed A., Gupta A., and Myung K. Mutator genes for suppression of gross chromosomal rearrangements identified by a genome-wide screening in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. U.S.A. 101 (2004) 9039-9044
92. Ball L.G., Zhang K., Cobb J.A., Boone C., and Xiao W. The yeast Shu complex couples error-free post-replication repair to homologous recombination. Mol. Microbiol. 73 (2009) 89-102
93. Lopes M., Cotta-Ramusino C., Pellicioli A., Liberi G., Plevani P., Muzi-Falconi M., Newlon C.S., and Foiani M. The DNA replication checkpoint response stabilizes stalled replication forks. Nature 412 (2001) 557-561
94. Sogo J.M., Lopes M., and Foiani M. Fork reversal and ssDNA accumulation at stalled replication forks owing to checkpoint defects. Science 297 (2002) 599-602
95. Gari K., Decaillet C., Delannoy M., Wu L., and Constantinou A. Remodeling of DNA replication structures by the branch point translocase FANCM. Proc. Natl. Acad. Sci. U.S.A. 105 (2008) 16107-16112
96. Gari K., Decaillet C., Stasiak A.Z., Stasiak A., and Constantinou A. The Fanconi anemia protein FANCM can promote branch migration of Holliday junctions and replication forks. Mol. Cell 29 (2008) 141-148
97. Kanagaraj R., Saydam N., Garcia P.L., Zheng L., and Janscak P. Human RECQ5beta helicase promotes strand exchange on synthetic DNA structures resembling a stalled replication fork. Nucleic Acids Res. 34 (2006) 5217-5231
98. Machwe A., Xiao L.R., Groden J., and Orren D.K. The Werner and Bloom syndrome proteins catalyze regression of a model replication fork. Biochemistry 45 (2006) 13939-13946
99. Ralf C., Hickson I.D., and Wu L. The Bloom's syndrome helicase can promote the regression of a model replication fork. J. Biol. Chem. 281 (2006) 22839-22846
100. Driscoll R., and Cimprich K.A. HARPing on about the DNA damage response during replication. Genes Dev. 23 (2009) 2359-2365