Control of genome stability by Slx protein complexes

Biochemical Society Transactions

Volumn 37, Issue 3, 2009, Pages 495-510

  Rouse, John ^a  

^a UNIVERSITY OF DUNDEE   (United Kingdom)

Author keywords

DNA damage; Mec1; Rad1; Sgs1; Slx; Tel1; Xeroderma pigmentosum complementation group F (XPF)

Indexed keywords

BRCA1 PROTEIN; ENDONUCLEASE; NUCLEASE; PROTEIN RAD1; PROTEIN RAD10; PROTEIN SLX; PROTEIN SLX1; PROTEIN SLX2; PROTEIN SLX3; PROTEIN SLX4; PROTEIN SLX5; PROTEIN SLX8; RECQ HELICASE; REPLISOME; RIBOSOME DNA; SUMO PROTEIN; UBIQUITIN PROTEIN LIGASE; UNCLASSIFIED DRUG;

ARTICLE; CATALYSIS; COMPLEX FORMATION; DNA ALKYLATION; DNA DAMAGE; DNA REPAIR; DNA REPLICATION; DOUBLE STRANDED DNA BREAK; ENZYME ACTIVITY; ENZYME PHOSPHORYLATION; ENZYME STRUCTURE; GENOMIC INSTABILITY; MOLECULAR MECHANICS; NONHUMAN; PRIORITY JOURNAL; PROTEIN CLEAVAGE; PROTEIN PROTEIN INTERACTION;

DNA DAMAGE; DNA REPAIR; DNA REPAIR ENZYMES; DNA REPLICATION; ENDODEOXYRIBONUCLEASES; ENDONUCLEASES; GENOME, FUNGAL; GENOMIC INSTABILITY; MODELS, BIOLOGICAL; RECQ HELICASES; SACCHAROMYCES CEREVISIAE; SACCHAROMYCES CEREVISIAE PROTEINS;

SACCHAROMYCES CEREVISIAE;

EID: 67649636091     PISSN: 03005127     EISSN: 14708752     Source Type: Journal    
DOI: 10.1042/BST0370495     Document Type: Article

References (178)

1. Bachrati, C.Z. and Hickson, I.D. (2008) RecQ helicases: guardian angels of the DNA replication fork. Chromosoma 117, 219-233
2. Bohr, V.A. (2008) Rising from the RecQ-age: the role of human RecQ helicases in genome maintenance. Trends Biochem. Sci. 33, 609-620
3. Yu, C.E., Oshima, J., Fu, Y.H., Wijsman, E.M., Hisama, F., Alisch, R., Matthews, S., Nakura, J., Miki, T., Ouais, S. et al. (1996) Positional cloning of the Werner's syndrome gene. Science 272, 258-262
4. Siitonen, H.A., Kaariainen, H. and Kestila, M. (2006) RECQL4: one gene behind three syndromes having an increased risk for cancers. FEBS J. 273 (Suppl. 1), 193
5. Van Maldergem, L., Siitonen, H.A., Jalkh, N., Chouery, E., De Roy, M., Delague, V., Muenke, M., Jabs, E.W., Cai, J., Wang, L.L. et al. (2006) Revisiting the craniosynostosis-radial ray hypoplasia association: Baller-Gerold syndrome caused by mutations in the RECQL4 gene. J. Med. Genet. 43, 148-152
6. Mohaghegh, P. and Hickson, I.D. (2001) DNA helicase deficiencies associated with cancer predisposition and premature ageing disorders. Hum. Mol. Genet. 10, 741-746
7. Ellis, N.A., Groden, J., Ye, T.Z., Straughen, J., Lennon, D.J., Ciocci, S., Proytcheva, M. and German, J. (1995) The Bloom's syndrome gene product is homologous to RecQ helicases. Cell 83, 655-666
8. Reference deleted
9. German, J. (1993) Bloom syndrome: a mendelian prototype of somatic mutational disease. Medicine 72, 393-406
10. Bachrati, C.Z. and Hickson, I.D. (2003) RecQ helicases: suppressors of tumorigenesis and premature aging. Biochem. J. 374, 577-606
11. Li, X. and Heyer, W.D. (2008) Homologous recombination in DNA repair and DNA damage tolerance. Cell Res. 18, 99-113
12. Pâques, F. and Haber, J.E. (1999) Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rev. 63, 349-404
13. Filippo, J.S., Sung, P. and Klein, H. (2008) Mechanism of eukaryotic homologous recombination. Annu. Rev. Biochem. 77, 229-257
14. West, S.C. (2003) Molecular views of recombination proteins and their control. Nat. Rev. Mol. Cell Biol. 4, 435-445
15. Chen, J.M., Cooper, D.N., Chuzhanova, N., Ferec, C. and Patrinos, G.P. (2007) Gene conversion: mechanisms, evolution and human disease. Nat. Rev. Genet. 8, 762-775
16. Szostak, J.W., Orrweaver, T.L., Rothstein, R.J. and Stahl, F.W. (1983) The double-strand-break repair model for recombination. Cell 33, 25-35
17. McGlynn, P. and Lloyd, R.G. (2002) Recombinational repair and restart of damaged replication forks. Nat. Rev. Mol. Cell Biol. 3, 859-870
18. Branzei, D. and Foiani, M. (2007) Interplay of replication checkpoints and repair proteins at stalled replication forks. DNA Repair 6, 994-1003
19. Tourriere, H. and Pasero, P. (2007) Maintenance of fork integrity at damaged DNA and natural pause sites. DNA Repair 6, 900-913
20. Reference deleted
21. Bashkirov, V.I., King, J.S., Bashkirova, E.V., Schmuckli-Maurer, J. and Heyer, W.-D. (2000) DNA repair protein Rad55 is a terminal substrate of the DNA damage checkpoints. Mol. Cell. Biol. 20, 4393-4404
22. Herzberg, K., Bashkirov, V.I., Rolfsmeier, M., Haghnazari, E., McDonald, W.H., Anderson, S., Bashkirova, E.V., Yates, III, J.R. and Heyer, W.-D. (2006) Phosphorylation of Rad55 on serines 2, 8, and 14 is required for efficient homologous recombination in the recovery of stalled replication forks. Mol. Cell. Biol. 26, 8396-8409
23. Wu, L. and Hickson, I.D. (2006) DNA helicases required for homologous recombination and repair of damaged replication forks. Annu. Rev. Genet. 40, 279-306
24. Reference deleted
25. Dong, Z. and Fasullo, M. (2003) Multiple recombination pathways for sister chromatid exchange in Saccharomyces cerevisiae: role of RAD1 and the RAD52 epistasis group genes. Nucleic Acids Res. 31, 2576-2585
26. Fasullo, M., Giallanza, P., Dong, Z., Cera, C. and Bennett, T. (2001) Saccharomyces cerevisiae Rad51 mutants are defective in DNA damage-associated sister chromatid exchanges but exhibit increased rates of homology-directed translocations. Genetics 158, 959-972
27. Kuzminov, A. (2001) DNA replication meets genetic exchange: chromosomal damage and its repair by homologous recombination. Proc. Natl. Acad. Sci. U.S.A. 98, 8461-8468
28. Reference deleted
29. Khakhar, R.R., Cobb, J.A., Bjergbaek, L., Hickson, I.D. and Gasser, S.M. (2003) RecQ helicases: multiple roles in genome maintenance. Trends Cell Biol. 13, 493-501
30. Liberi, G., Maffioletti, G., Lucca, C., Chiolo, I., Baryshnikova, A., Cotta-Ramusino, C., Lopes, M., Pellicioli, A., Haber, J.E. and Foiani, M. (2005) Rad51-dependent DNA structures accumulate at damaged replication forks in sgs1 mutants defective in the yeast ortholog of BLM RecQ helicase. Genes Dev. 19, 339-350
31. Wu, L. and Hickson, I.D. (2001) RecQ helicases and topoisomerases: components of a conserved complex for the regulation of genetic recombination. Cell. Mol. Life Sci. 58, 894-901
32. Watt, P.M., Hickson, I.D., Borts, R.H. and Louis, E.J. (1996) SGS1, a homologue of the Bloom's and Werner's syndrome genes, is required for maintenance of genome stability in Saccharomyces cerevisiae. Genetics 144, 935-945
33. Fricke, W.M., Kaliraman, V. and Brill, S.J. (2001) Mapping the DNA topoisomerase III binding domain of the Sgs1 DNA helicase. J. Biol. Chem. 276, 8848-8855
34. Gangloff, S., McDonald, J.P., Bendixen, C., Arthur, L. and Rothstein, R. (1994) The yeast type I topoisomerase Top3 interacts with Sgs1, a DNA helicase homolog: a potential eukaryotic reverse gyrase. Mol. Cell. Biol. 14, 8391-8398
35. Murray, J.M., Lindsay, H.D., Munday, C.A. and Carr, A.M. (1997) Role of Schizosaccharomyces pombe RecQ homolog, recombination, and checkpoint genes in UV damage tolerance. Mol. Cell. Biol. 17, 6868-6875
36. Wallis, J.W., Chrebet, G., Brodsky, G., Rolfe, M. and Rothstein, R. (1989) A hyper-recombination mutation in S. cerevisiae identifies a novel eukaryotic topoisomerase. Cell 58, 409-419
37. Mankouri, H.W. and Hickson, I.D. (2007) The RecQ helicase-topoisomerase III-Rmi1 complex: a DNA structure-specific 'dissolvasome'? Trends Biochem. Sci. 32, 538-546
38. Wu, L. and Hickson, I.D. (2003) The Bloom's syndrome helicase suppresses crossing over during homologous recombination. Nature 426, 870-874
39. Mullen, J.R., Kaliraman, V., Ibrahim, S.S. and Brill, S.J. (2001) Requirement for three novel protein complexes in the absence of the Sgs1 DNA helicase in Saccharomyces cerevisiae. Genetics 157, 103-118
40. Interthal, H. and Heyer, W.D. (2000) MUS81 encodes a novel helix-hairpin-helix protein involved in the response to UV- and methylation-induced DNA damage in Saccharomyces cerevisiae. Mol. Gen. Genet. 263, 812-827
41. Boddy, M.N., Lopez-Girona, A., Shanahan, P., Interthal, H., Heyer, W.D. and Russell, P. (2000) Damage tolerance protein Mus81 associates with the FHA1 domain of checkpoint kinase Cds1. Mol. Cell. Biol. 20, 8758-8766
42. Chen, X.B., Melchionna, R., Denis, C.M., Gaillard, P.H.L., Blasina, A., Van de Weyer, I., Boddy, M.N., Russell, P., Vialard, J. and McGowan, C.H. (2001) Human Mus81-associated endonuclease cleaves Holliday junctions in vitro. Mol. Cell 8, 1117-1127
43. Boddy, M.N., Gaillard, P.H., McDonald, W.H., Shanahan, P., Yates, 3rd, J.R. and Russell, P. (2001) Mus81-Eme1 are essential components of a Holliday junction resolvase. Cell 107, 537-548
44. Kaliraman, V., Mullen, J.R., Fricke, W.M., Bastin-Shanower, S.A. and Brill, S.J. (2001) Functional overlap between Sgs1-Top3 and the Mms4-Mus81 endonuclease. Genes Dev. 15, 2730-2740
45. Ciccia, A., McDonald, N. and West, S.C. (2008) Structural and functional relationships of the XPF/MUS81 family of proteins. Annu. Rev. Biochem. 77, 259-287
46. Osman, F. and Whitby, M.C. (2007) Exploring the roles of Mus81-Eme1/Mms4 at perturbed replication forks. DNA Repair 6, 1004-1017
47. Bastin-Shanower, S.A., Fricke, W.M., Mullen, J.R. and Brill, S.J. (2003) The mechanism of Mus81-Mms4 cleavage site selection distinguishes it from the homologous endonuclease Rad1-Rad10. Mol. Cell. Biol. 23, 3487-3496
48. Hanada, K., Budzowska, M., Davies, S.L., van Drunen, E., Onizawa, H., Beverloo, H.B., Maas, A., Essers, J., Hickson, I.D. and Kanaar, R. (2007) The structure-specific endonuclease Mus81 contributes to replication restart by generating double-strand DNA breaks. Nat. Struct. Mol. Biol. 14, 1096-1104
49. Hanada, K., Budzowska, M., Modesti, M., Maas, A., Wyman, C., Essers, J. and Kanaar, R. (2006) The structure-specific endonuclease Mus81-Eme1 promotes conversion of interstrand DNA crosslinks into double-strands breaks. EMBO J. 25, 4921-4932
50. Schwartz, A.L. and Ciechanover, A. (2009) Targeting proteins for destruction by the ubiquitin system: implications for human pathobiology. Annu. Rev. Pharmacol. Toxicol. 49, 73-96
51. Geiss-Friedlander, R. and Melchior, F. (2007) Concepts in sumoylation: a decade on. Nat. Rev. Mol. Cell Biol. 8, 947-956
52. Wilson, V.G. and Heaton, P.R. (2008) Ubiquitin proteolytic system: focus on SUMO. Expert Rev. Proteomics 5, 121-135
53. Li, T., Fung, J., Mullen, J.R. and Brill, S.J. (2007) The yeast Slx5-Slx8 DNA integrity complex displays ubiquitin ligase activity. Cell Cycle 6, 2800-2809
54. Xie, Y., Kerscher, O., Kroetz, M.B., McConchie, H.F., Sung, P. and Hochstrasser, M. (2007) The yeast Hex3.Slx8 heterodimer is a ubiquitin ligase stimulated by substrate sumoylation. J. Biol. Chem. 282, 34176-34184
55. Uzunova, K., Gottsche, K., Miteva, M., Weisshaar, S.R., Glanemann, C., Schnellhardt, M., Niessen, M., Scheel, H., Hofmann, K., Johnson, E.S. et al. (2007) Ubiquitin-dependent proteolytic control of SUMO conjugates. J. Biol. Chem. 282, 34167-34175
56. Li, T., Mullen, J.R., Slagle, C.E. and Brill, S.J. (2007) Stimulation of in vitro sumoylation by Slx5-Slx8: Evidence for a functional interaction with the SUMO pathway. DNA Repair 6, 1679-1691
57. Mullen, J.R. and Brill, S.J. (2008) Activation of the Slx5-Slx8 ubiquitin ligase by poly-small ubiquitin-like modifier conjugates. J. Biol. Chem. 283, 19912-19921
58. Darst, R.P., Garcia, S.N., Koch, M.R. and Pillus, L. (2008) Slx5 promotes transcriptional silencing and is required for robust growth in the absence of Sir2. Mol. Cell. Biol. 28, 1361-1372
59. Johnson, E.S. and Blobel, G. (1999) Cell cycle-regulated attachment of the ubiquitin-related protein SUMO to the yeast septins. J. Cell Biol. 147, 981-993
60. Li, S.J. and Hochstrasser, M. (1999) A new protease required for cell-cycle progression in yeast. Nature 398, 246-251
61. Bachant, J., Alcasabas, A., Blat, Y., Kleckner, N. and Elledge, S.J. (2002) The SUMO-1 isopeptidase Smt4 is linked to centromeric cohesion through SUMO-1 modification of DNA topoisomerase II. Mol. Cell 9, 1169-1182
62. Stead, K., Aguilar, C., Hartman, T., Drexel, M., Meluh, P. and Guacci, V. (2003) Pds5p regulates the maintenance of sister chromatid cohesion and is sumoylated to promote the dissolution of cohesion. J. Cell Biol. 163, 729-741
63. Burgess, R.C., Rahman, S., Lisby, M., Rothstein, R. and Zhao, X.L. (2007) The slx5-slx8 complex affects sumoylation of DNA repair proteins and negatively regulates recombination. Mol. Cell. Biol. 27, 6153-6162
64. Sacher, M., Pfander, B., Hoege, C. and Jentsch, S. (2006) Control of Rad52 recombination activity by double-strand break-induced SUMO modification. Nat. Cell Biol. 8, 1284-1290
65. Fabre, F., Chan, A., Heyer, W.D. and Gangloff, S. (2002) Alternate pathways involving Sgs1/Top3, Mus81/Mms4, and Srs2 prevent formation of toxic recombination intermediates from single-stranded gaps created by DNA replication. Proc. Natl. Acad. Sci. U.S.A. 99, 16887-16892
66. Pan, X.W., Ye, P., Yuan, D.S., Wang, X.L., Bader, J.S. and Boeke, J.D. (2006) A DNA integrity network in the yeast Saccharomyces cerevisiae. Cell 124, 1069-1081
67. Prudden, J., Pebernard, S., Raffa, G., Slavin, D.A., Perry, J.J.P., Tainer, J.A., McGowan, C.H. and Boddy, M.N. (2007) SUMO-targeted ubiquitin ligases in genome stability. EMBO J. 26, 4089-4101
68. Sun, H., Leverson, J.D. and Hunter, T. (2007) Conserved function of RNF4 family proteins in eukaryotes: targeting a ubiquitin ligase to SUMOylated proteins. EMBO J. 26, 4102-4112
69. Morishita, T., Tsutsui, Y., Iwasaki, H. and Shinagawa, H. (2003) The Schizosaccharomyces pombe rad60 gene is essential for repairing double-strand DNA breaks spontaneously occurring during replication and induced by DNA-damaging agents. Mol. Cell. Biol. 22, 3537-3548
70. Miyabe, I., Morishita, T., Hishida, T., Yonei, S. and Shinagawa, H. (2006) Rhp51-dependent recombination intermediates that do not generate checkpoint signal are accumulated in Schizosaccharomyces pombe rad60 and smc5/6 mutants after release from replication arrest. Mol. Cell. Biol. 26, 343-353
71. Raffa, G.D., Wohlschlegel, J., Yates, J.R. and Boddy, M.N. (2006) SUMO-binding motifs mediate the Rad60-dependent response to replicative stress and self-association. J. Biol. Chem. 281, 27973-27981
72. Tatham, M.H., Geoffroy, M.C., Shen, L., Plechanovova, A., Hattersley, N., Jaffray, E.G., Palvimo, J.J. and Hay, R.T. (2008) RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation. Nat. Cell Biol. 10, 538-546
73. 3 induces NB4 cell apoptosis with downregulation of bcl-2 expression and modulation of PML-RARα/PML proteins. Blood 88, 1052-1061
74. 3-induced PML or PML/retinoic acid receptor α degradation. J. Exp. Med. 193, 1361-1371
75. Muller, S., Miller, W.H. and Dejean, A. (1998) Trivalent antimonials induce degradation of the PML-RARα oncoprotein and reorganization of the promyelocytic leukemia nuclear bodies in acute promyelocytic leukemia NB4 cells. Blood 92, 4308-4316
76. Shao, W.L., Fanelli, M., Ferrara, F.F., Riccioni, R., Rosenauer, A., Davison, K., Lamph, W.W., Waxman, S., Pelicci, P.G., Lo Coco, F. et al. (1998) Arsenic trioxide as an inducer of apoptosis and loss of PML /RARα protein in acute promyelocytic leukemia cells. J. Natl. Cancer Inst. 90, 124-133
77. Zhu, J., Koken, M.H.M., Quignon, F., Chelbi Alix, M.K., Degos, L., Wang, Z.Y., Chen, Z. and de Thé, H. (1997) Arsenic-induced PML targeting onto nuclear bodies: implications for the treatment of acute promyelocytic leukemia. Proc. Natl. Acad. Sci. U.S.A. 94, 3978-3983
78. Sternsdorf, T., Puccetti, E., Jensen, K., Hoelzer, D., Will, H., Ottmann, O.G. and Ruthardt, M. (1999) PIC-1/SUMO-1-modified PML-retinoic acid receptor α mediates arsenic trioxide-induced apoptosis in acute promyelocytic leukemia. Mol. Cell. Biol. 19, 5170-5178
79. Lallemand-Breitenbach, V., Jeanne, M., Benhenda, S., Nasr, R., Lei, M., Peres, L., Zhou, J., Zhu, J., Raught, B. and de Thé, H. (2008) Arsenic degrades PML or PML-RAR α through a SUMO-triggered RNF4/ ubiquitin-mediated pathway. Nat. Cell Biol. 10, 547-555
80. Aravind, L. and Koonin, E.V. (2001) Prokaryotic homologs of the eukaryotic DNA-end-binding protein Ku, novel domains in the Ku protein and prediction of a prokaryotic double-strand break repair system. Genome Res. 11, 1365-1374
81. Legrand, M., Chan, C.L., Jauert, P.A. and Kirkpatrick, D.T. (2008) Analysis of base excision and nucleotide excision repair in Candida albicans. Microbiology 154, 2446-2456
82. Dunin-Horkawicz, S., Feder, M. and Bujnicki, J.M. (2006) Phylogenomic analysis of the GIY-YIG nuclease superfamily. BMC Genomics 7, 98
83. Kowalski, J.C., Belfort, M., Stapleton, M.A., Holpert, M., Dansereau, J.T., Pietrokovski, S., Baxter, S.M. and Derbyshire, V. (1999) Configuration of the catalytic GIY-YIG domain of intron endonuclease I-Tevl: coincidence of computational and molecular findings. Nucleic Acids Res. 27, 2115-2125
84. Aravind, L. and Koonin, E.V. (2000) SAP: a putative DNA-binding motif involved in chromosomal organization. Trends Biochem. Sci. 25, 112-114
85. Huttner, D. and Ulrich, H.D. (2008) Cooperation of replication protein A with the ubiquitin ligase Rad18 in DNA damage bypass. Cell Cycle 7, 3629-3633
86. Coulon, S., Gaillard, P.H., Chahwan, C., McDonald, W.H., Yates, 3rd, J.R. and Russell, P. (2004) Slx1-Slx4 are subunits of a structure-specific endonuclease that maintains ribosomal DNA in fission yeast. Mol. Biol. Cell 15, 71-80
87. Fricke, W.M. and Brill, S.J. (2003) Slx1-Slx4 is a second structure-specific endonuclease functionally redundant with Sgs1-Top3. Genes Dev. 17, 1768-1778
88. Petes, T.D. (1979) Yeast ribosomal DNA genes are located on chromosome XII. Proc. Natl. Acad. Sci. U.S.A. 76, 410-414
89. Rustchenko, E.P., Curran, T.M. and Sherman, F. (1993) Variations in the number of ribosomal DNA units in morphological mutants and normal strains of Candida albicans and in normal strains of Saccharomyces cerevisiae. J. Bacteriol. 175, 7189-7199
90. Petrie, K. and Zelent, A. (2008) Marked for death. Nat. Cell Biol. 10, 507-509
91. Szostak, J.W. and Wu, R. (1980) Unequal crossing over in the ribosomal DNA of Saccharomyces cerevisiae. Nature 284, 426-430
92. Tsang, E. and Carr, A.M. (2008) Replication fork arrest, recombination and the maintenance of ribosomal DNA stability. DNA Repair 7, 1613-1623
93. Brewer, B.J. and Fangman, W.L. (1988) A replication fork barrier at the 3′ end of yeast ribosomal-RNA genes. Cell 55, 637-643
94. Skryabin, K.G., Eldarov, M.A., Larionov, V.L., Bayev, A.A., Klootwijk, J., Deregt, V.C.H.F., Veldman, G.M., Planta, R.J., Georgiev, O.I. and Hadjiolov, A.A. (1984) Structure and function of the nontranscribed spacer regions of yeast rDNA. Nucleic Acids Res. 12, 2955-2968
95. Linskens, M.H.K. and Huberman, J.A. (1988) Organization of replication of ribosomal DNA in Saccharomyces cerevisiae. Mol. Cell. Biol. 8, 4927-4935
96. Walmsley, R.M., Johnston, L.H., Williamson, D.H. and Oliver, S.G. (1984) Replicon size of yeast ribosomal DNA. Mol. Gen. Genet. 195, 260-266
97. Kaliraman, V. and Brill, S.J. (2002) Role of SGS1 and SLX4 in maintaining rDNA structure in Saccharomyces cerevisiae. Curr. Genet. 41, 389-400
98. Hennessy, K.M., Lee, A., Chen, E. and Botstein, D. (1991) A group of interacting yeast DNA replication genes. Genes Dev. 5, 958-969
99. 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
100. Rad52-dependent repair of ribosomal DNA repeats cleaved by Slx1-Slx4 endonuclease. Mol. Biol. Cell 17, 2081-2090
101. Ivessa, A.S., Lenzmeier, B.A., Bessler, J.B., Goudsouzian, L.K., Schnakenberg, S.L. and Zakian, V.A. (2003) The Saccharomyces cerevisiae helicase Rrm3p facilitates replication past nonhistone protein-DNA complexes. Mol. Cell 12, 1525-1536
102. Chang, M., Bellaoui, M., Boone, C. and Brown, G.W. (2002) A genome-wide screen for methyl methanesulfonate-sensitive mutants reveals genes required for S phase progression in the presence of DNA damage. Proc. Natl. Acad. Sci. U.S.A. 99, 16934-16939
103. Hanway, D., Chin, J.K., Xia, G., Oshiro, G., Winzeler, E.A. and Romesberg, F.E. (2002) Previously uncharacterized genes in the UV-and MMS-induced DNA damage response in yeast. Proc. Natl. Acad. Sci. U.S.A. 99, 10605-10610
104. Flott, S. and Rouse, J. (2005) Slx4 becomes phosphorylated after DNA damage in a Mec1/Tel1-dependent manner and is required for repair of DNA alkylation damage. Biochem. J. 391, 325-333
105. Flott, S., Alabert, C., Toh, G.W., Toth, R., Sugawara, N., Campbell, D.G., Haber, J.E., Pasero, P. and Rouse, J. (2007) Phosphorylation of Slx4 by mec1 and tel1 regulates the single-strand annealing mode of DNA repair in budding yeast. Mol. Cell. Biol. 27, 6433-6445
106. Beranek, D.T. (1990) Distribution of methyl and ethyl adducts following alkylation with monofunctional alkylating agents. Mutat. Res. 231, 11-30
107. 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
108. Wang, Z. (2001) Translesion synthesis by the UmuC family of DNA polymerases. Mutat. Res. 486, 59-70
109. Friedberg, E.C. (2005) Suffering in silence: the tolerance of DNA damage. Nat. Rev. Mol. Cell Biol. 6, 943-953
110. Ulrich, H.D. (2005) The RAD6 pathway: control of DNA damage bypass and mutagenesis by ubiquitin and SUMO. Chembiochem 6, 1735-1743
111. Barbour, L. and Xiao, W. (2003) Regulation of alternative replication bypass pathways at stalled replication forks and its effects on genome stability: a yeast model. Mutat. Res. 532, 137-155
112. Prakash, L. (1981) Characterization of postreplication repair in Saccharomyces cerevisiae and effects of rad6, rad18, rev3 and rad52 mutations. Mol. Gen. Genet. 184, 471-478
113. Jentsch, S., McGrath, J.P. and Varshavsky, A. (1987) The yeast DNA repair gene RAD6 encodes a ubiquitin-conjugating enzyme. Nature 329, 131-134
114. Bailly, V., Lauder, S., Prakash, S. and Prakash, L. (1997) Yeast DNA repair proteins Rad6 and Rad18 form a heterodimer that has ubiquitin conjugating, DNA binding, and ATP hydrolytic activities. J. Biol. Chem. 272, 23360-23365
115. Bailly, V., Lamb, J., Sung, P., Prakash, S. and Prakash, L. (1994) Specific complex formation between yeast RAD6 and RAD18 proteins: a potential mechanism for targeting RAD6 ubiquitin-conjugating activity to DNA damage sites. Genes Dev. 8, 811-820
116. Hoege, C., Pfander, B., Moldovan, G.L., Pyrowolakis, G. and Jentsch, S. (2002) RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO. Nature 419, 135-141
117. Haracska, L., Torres-Ramos, C.A., Johnson, R.E., Prakash, S. and Prakash, L. (2004) Opposing effects of ubiquitin conjugation and SUMO modification of PCNA on replicational bypass of DNA lesions in Saccharomyces cerevisiae. Mol. Cell. Biol. 24, 4267-4274
118. Prakash, S., Johnson, R.E. and Prakash, L. (2005) Eukaryotic translesion synthesis DNA polymerases: specificity of structure and function. Annu. Rev. Biochem. 74, 317-353
119. Kannouche, P.L. and Lehmann, A.R. (2004) Ubiquitination of PCNA and the polymerase switch in human cells. Cell Cycle 3, 1011-1013
120. Bienko, M., Green, C.M., Crosetto, N., Rudolf, F., Zapart, G., Coull, B., Kannouche, P., Wider, G., Peter, M., Lehmann, A.R. et al. (2005) Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis. Science 310, 1821-1824
121. Johnson, R.E., Prakash, S. and Prakash, L. (1999) Efficient bypass of a thymine-thymine dimer by yeast DNA polymerase, Poleta. Science 283, 1001-1004
122. Washington, M.T., Johnson, R.E., Prakash, S. and Prakash, L. (2000) Accuracy of thymine-thymine dimer bypass by Saccharomyces cerevisiae DNA polymerase η. Proc. Natl. Acad. Sci. U.S.A. 97, 3094-3099
123. Lawrence, C.W. and Maher, V.M. (2001) Mutagenesis in eukaryotes dependent on DNA polymerase ζ and Rev1p. Philos. Trans. R. Soc. London Ser. B 356, 41-46
124. Torres-Ramos, C.A., Prakash, S. and Prakash, L. (2002) Requirement of RAD5 and MMS2 for postreplication repair of UV-damaged DNA in Saccharomyces cerevisiae. Mol. Cell. Biol. 22, 2419-2426
125. Hofmann, R.M. and Pickart, C.M. (1999) Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair. Cell 96, 645-653
126. Ulrich, H.D. and Jentsch, S. (2000) Two RING finger proteins mediate cooperation between ubiquitin-conjugating enzymes in DNA repair. EMBO J. 19, 3388-3397
127. Higgins, N.P., Kato, K. and Strauss, B. (1976) A model for replication repair in mammalian cells. J. Mol. Biol. 101, 417-425
128. Lawrence, C. (1994) The RAD6 DNA repair pathway in Saccharomyces cerevisiae: what does it do, and how does it do it? BioEssays 16, 253-258
129. Zappulla, D.C., Maharaj, A.S., Connelly, J.J., Jockusch, R.A. and Sternglanz, R. (2006) Rtt107/Esc4 binds silent chromatin and DNA repair proteins using different BRCT motifs. BMC Mol. Biol. 7, 40
130. Callebaut, I. and Mornon, J.P. (1997) From BRCA1 to RAP1: a widespread BRCT module closely associated with DNA repair. FEBS Lett. 400, 25-30
131. Bork, P., Hofmann, K., Bucher, P., Neuwald, A.F., Altschul, S.F. and Koonin, E.V. (1997) A superfamily of conserved domains in DNA damage-responsive cell cycle checkpoint proteins. FASEB J. 11, 68-76
132. Scholes, D.T., Banerjee, M., Bowen, B. and Curcio, M.J. (2001) Multiple regulators of Ty1 transposition in Saccharomyces cerevisiae have conserved roles in genome maintenance. Genetics 159, 1449-1465
133. Rouse, J. (2004) Esc4p, a new target of Mec1p (ATR), promotes resumption of DNA synthesis after DNA damage. EMBO J. 23, 1188-1197
134. 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 phosphorylation of the BRCT checkpoint-dependent domain protein Rtt107/Esc4. Mol. Biol. Cell 17, 539-548
135. Rouse, J. (2004) Esc4p, a new target of Mec1p (ATR), promotes resumption of DNA synthesis after DNA damage. EMBO J. 23, 1188-1197
136. Tong, A.H.Y., Lesage, G., Bader, G.D., Ding, H.M., Xu, H., Xin, X.F., Young, J., Berriz, G.F., Brost, R.L., Chang, M. et al. (2004) Global mapping of the yeast genetic interaction network. Science 303, 808-813
137. Tong, A.H., Evangelista, M., Parsons, A.B., Xu, H., Bader, G.D., Page, N., Robinson, M., Raghibizadeh, S., Hogue, C.W., Bussey, H. et al. (2001) Systematic genetic analysis with ordered arrays of yeast deletion mutants. Science 294, 2364-2368
138. Sheedy, D.M., Dimitrova, D., Rankin, J.K., Bass, K.L., Lee, K.M., Tapia-Alveal, C., Harvey, S.H., Murrar, J.M. and O'Connell, M.J. (2005) Brcl-mediated DNA repair and damage tolerance. Genetics 171, 457-468
139. Losada, A. and Hirano, T. (2005) Dynamic molecular linkers of the genome: the first decade of SMC proteins. Genes Dev. 19, 1269-1287
140. Murray, J.M. and Carr, A.M. (2008) Smc5/6: a link between DNA repair and unidirectional replication? Nat. Rev. Mol. Cell Biol. 9, 177-182
141. Ito, T., Chiba, T., Ozawa, R., Yoshida, M., Hattori, M. and Sakaki, Y. (2001) A comprehensive two-hybrid analysis to explore the yeast protein interactome. Proc. Natl. Acad. Sci. U.S.A. 98, 4569-4574
142. Tsodikov, O.V., Enzlin, J.H., Scharer, O.D. and Ellenberger, T. (2005) Crystal structure and DNA binding functions of ERCC1, a subunit of the DNA structure-specific endonuclease XPF-ERCC1. Proc. Natl. Acad. Sci. U.S.A. 102, 11236-11241
143. Tripsianes, K., Folkers, G., Ab, E., Das, D., Odijk, H., Jaspers, N.G.J., Hoeijmakers, J.H.J., Kaptein, R. and Boelens, R. (2005) The structure of the human ERCC1/XPF interaction domains reveals a complementary role for the two proteins in nucleotide excision repair. Structure 13, 1849-1858
144. Tomkinson, A.E., Bardwell, A.J., Bardwell, L., Tappe, N.J. and Friedberg, E.C. (1993) Yeast DNA-repair and recombination proteins Rad1 and Rad10 constitute a single-stranded-DNA endonuclease. Nature 362, 860-862
145. Bardwell, A.J., Bardwell, L., Johnson, D.K. and Friedberg, E.C. (1993) Yeast DNA recombination and repair proteins Rad1 and Rad10 constitute a complex in vivo mediated by localized hydrophobic domains. Mol. Microbiol. 8, 1177-1188
146. Bardwell, A.J., Bardwell, L., Tomkinson, A.E. and Friedberg, E.C. (1994) Specific cleavage of model recombination and repair intermediates by the yeast Rad1-Rad10 DNA endonuclease. Science 265, 2082-2085
147. Davies, A.A., Friedberg, E.C., Tomkinson, A.E., Wood, R.D. and West, S.C. (1995) Role of the Rad1 and Rad10 proteins in nucleotide excision-repair and recombination. J. Biol. Chem. 270, 24638-24641
148. Rodriguez, K., Wang, Z.G., Friedberg, E.C. and Tomkinson, A.E. (1996) Identification of functional domains within the RAD1-RAD10 repair and recombination endonuclease of Saccharomyces cerevisiae. J. Biol. Chem. 271, 20551-20558
149. Costa, R.M.A., Chigancas, V., Galhardo, R.D., Carvalho, H. and Menck, C.F.M. (2003) The eukaryotic nucleotide excision repair pathway. Biochimie 85, 1083-1099
150. de Laat, W.L., Jaspers, N.G.J. and Hoeijmakers, J.H.J. (1999) Molecular mechanism of nucleotide excision repair. Genes Dev. 13, 768-785
151. Prakash, S. and Prakash, L. (2000) Nucleotide excision repair in yeast. Mutat. Res. 451, 13-24
152. Fishman-Lobell, J. and Haber, J.E. (1992) Removal of nonhomologous DNA ends in double-strand break recombination: the role of the yeast ultraviolet repair gene RAD1. Science 258, 480-484
153. Bardwell, L., Cooper, A.J. and Friedberg, E.C. (1992) Stable and specific association between the yeast recombination and DNA repair proteins RAD1 and RAD10 in vitro. Mol. Cell. Biol. 12, 3041-3049
154. Schiestl, R.H. and Prakash, S. (1988) RAD1, an excision repair gene of Saccharomyces cerevisiae, is also involved in recombination. Mol. Cell. Biol. 8, 3619-3626
155. Ivanov, E.L. and Haber, J.E. (1995) Rad1 and Rad10, but not other excision-repair genes, are required for double-strand break-induced recombination in Saccharomyces cerevisiae. Mol. Cell. Biol. 15, 2245-2251
156. Pâques, F. and Haber, J.E. (1997) Two pathways for removal of nonhomologous DNA ends during double-strand break repair in Saccharomyces cerevisiae. Mol. Cell. Biol. 17, 6765-6771
157. Sugawara, N., Pâques, F., Colaiacovo, M. and Haber, J.E. (1997) Role of Saccharomyces cerevisiae Msh2 and Msh3 repair proteins in double-strand break-induced recombination. Proc. Natl. Acad. Sci. U.S.A. 94, 9214-9219
158. Colaiacovo, M.P., Pâques, F. and Haber, J.E. (1999) Removal of one nonhomologous DNA end during gene conversion by a RAD1- and MSH2-independent pathway. Genetics 151, 1409-1423
159. Saparbaev, M., Prakash, L. and Prakash, S. (1996) Requirement of mismatch repair genes MSH2 and MSH3 in the RAD1-RAD10 pathway of mitotic recombination in Saccharomyces cerevisiae. Genetics 142, 727-736
160. Evans, E., Sugawara, N., Haber, J.E. and Alani, E. (2000) The Saccharomyces cerevisiae Msh2 mismatch repair protein localizes to recombination intermediates in vivo. Mol. Cell 5, 789-799
161. Sugawara, N., Ira, G. and Haber, J.E. (2000) DNA length dependence of the single-strand annealing pathway and the role of Saccharomyces cerevisiae RAD59 in double-strand break repair. Mol. Cell. Biol. 20, 5300-5309
162. Lyndaker, A.M., Goldfarb, T. and Alani, E. (2008) Mutants defective in Rad1-Rad10-Slx4 exhibit a unique pattern of viability during mating-type switching in Saccharomyces cerevisiae. Genetics 179, 1807-1821
163. Holmes, A.M. and Haber, J.E. (1999) Double-strand break repair in yeast requires both leading and lagging strand DNA polymerases. Cell 96, 415-424
164. Li, F.Y., Dong, J.C., Pan, X.W., Oum, J.H., Boeke, J.D. and Lee, S.E. (2008) Microarray-based genetic screen defines SAW1, a gene required for Rad1/Rad10-dependent processing of recombination intermediates. Mol. Cell 30, 325-335
165. Haber, J.E. (1998) Mating-type gene switching in Saccharomyces cerevisiae. Annu. Rev. Genet. 32, 561-599
166. Hwang, J.Y., Smith, S. and Myung, K. (2005) The Rad1-Rad10 complex promotes the production of gross chromosomal rearrangements from spontaneous DNA damage in Saccharomyces cerevisiae. Genetics 169, 1927-1937
167. Newman, M., Murray-Rust, J., Lally, J., Rudolf, J., Fadden, A., Knowles, P.P., White, M.F. and McDonald, N.Q. (2005) Structure of an XPF endonuclease with and without DNA suggests a model for substrate recognition. EMBO J. 24, 895-905
168. Carr, A.M. (2002) DNA structure dependent checkpoints as regulators of DNA repair. DNA Repair 1, 983-994
169. Harrison, J.C. and Haber, J.E. (2006) Surviving the breakup: the DNA damage checkpoint. Annu. Rev. Genet. 40, 209-235
170. Shiloh, Y. (2006) The ATM-mediated DNA-damage response: taking shape. Trends Biochem. Sci. 31, 402-410
171. Cimprich, K.A. and Cortez, D. (2008) ATR: an essential regulator of genome integrity. Nat. Rev. Mol. Cell Biol. 9, 616-627
172. de Klein, A., Muijtjens, M., van Os, R., Verhoeven, Y., Smit, B., Carr, A.M., Lehmann, A.R. and Hoeijmakers, J.H.J. (2000) Targeted disruption of the cell-cycle checkpoint gene ATR leads to early embryonic lethality in mice. Curr. Biol. 10, 479-482
173. Kato, R. and Ogawa, H. (1994) An essential gene, Esr1, is required for mitotic cell growth, DNA repair and meiotic recombination in Saccharomyces cerevisiae. Nucleic Acids Res. 22, 3104-3112
174. Brown, E.J. and Baltimore, D. (2000) ATR disruption leads to chromosomal fragmentation and early embryonic lethality. Genes Dev. 14, 397-402
175. Zhao, X.L., Muller, E.G.D. and Rothstein, R. (1998) A suppressor of two
176. Lavin, M.F. (2008) Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer. Nat. Rev. Mol. Cell Biol. 9, 759-769
177. Traven, A. and Heierhorst, J. (2005) SQ/TQ cluster domains: concentrated ATM/ATR kinase phosphorylation site regions in DNA-damage-response proteins. BioEssays 27, 397-407
178. Shiloh, Y. (2003) ATM and related protein kinases: safeguarding genome integrity. Nat. Rev. Cancer 3, 155-168