Homologous recombination is a universal mechanism that allows DNA repair and ensures the efficiency of DNA replication. The substrate initiating the process of homologous recombination is a single-stranded DNA that promotes a strand exchange reaction resulting in a genetic exchange that promotes genetic diversity and DNA repair. The molecular mechanisms by which homologous recombination repairs a double-strand break have been extensively studied and are now well characterized. However, the mechanisms by which homologous recombination contribute to DNA replication in eukaryotes remains poorly understood. Studies in bacteria have identified multiple roles for the machinery of homologous recombination at replication forks. Here, we review our understanding of the molecular pathways involving the homologous recombination machinery to support the robustness of DNA replication. In addition to its role in fork-recovery and in rebuilding a functional replication fork apparatus, homologous recombination may also act as a fork-protection mechanism. We discuss that some of the fork-escort functions of homologous recombination might be achieved by loading of the recombination machinery at inactivated forks without a need for a strand exchange step; as well as the consequence of such a model for the stability of eukaryotic genomes.
References
[1]
West, S.C. Molecular views of recombination proteins and their control. Natl. Rev. Mol. Cell Biol. 2003, 4, 435–445, doi:10.1038/nrm1127.
[2]
Cox, M.M. Regulation of bacterial reca protein function. Crit. Rev. Biochem. Mol. Biol. 2007, 42, 41–63, doi:10.1080/10409230701260258.
[3]
Krejci, L.; Altmannova, V.; Spirek, M.; Zhao, X. Homologous recombination and its regulation. Nucleic Acids Res. 2012, 40, 5795–5818.
[4]
Deakyne, J.S.; Mazin, A.V. Fanconi anemia: At the crossroads of DNA repair. Biochem. Biokhimiia 2011, 76, 36–48, doi:10.1134/S0006297911010068.
[5]
Michel, B.; Boubakri, H.; Baharoglu, Z.; LeMasson, M.; Lestini, R. Recombination proteins and rescue of arrested replication forks. DNA Repair 2007, 6, 967–980, doi:10.1016/j.dnarep.2007.02.016.
[6]
Costanzo, V. Brca2, rad51 and mre11: Performing balancing acts on replication forks. DNA Repair 2011, 10, 1060–1065.
[7]
Courcelle, J.; Hanawalt, P.C. Reca-dependent recovery of arrested DNA replication forks. Annu. Rev. Genet. 2003, 37, 611–646, doi:10.1146/annurev.genet.37.110801.142616.
Heller, R.C.; Marians, K.J. Replication fork reactivation downstream of a blocked nascent leading strand. Nature 2006, 439, 557–562.
[10]
Heller, R.C.; Marians, K.J. Replisome assembly and the direct restart of stalled replication forks. Nat. Rev. Mol. Cell Biol. 2006, 7, 932–943, doi:10.1038/nrm2058.
[11]
Gabbai, C.B.; Marians, K.J. Recruitment to stalled replication forks of the pria DNA helicase and replisome-loading activities is essential for survival. DNA Repair 2010, 9, 202–209, doi:10.1016/j.dnarep.2009.12.009.
[12]
Heller, R.C.; Marians, K.J. The disposition of nascent strands at stalled replication forks dictates the pathway of replisome loading during restart. Mol. Cell 2005, 17, 733–743.
[13]
Kowalczykowski, S.C. Initiation of genetic recombination and recombination-dependent replication. Trends Biochem. Sci. 2000, 25, 156–165, doi:10.1016/S0968-0004(00)01569-3.
[14]
Lusetti, S.L.; Cox, M.M. The bacterial reca protein and the recombinational DNA repair of stalled replication forks. Annu. Rev. Biochem. 2002, 71, 71–100, doi:10.1146/annurev.biochem.71.083101.133940.
[15]
Kuzminov, A. DNA replication meets genetic exchange: Chromosomal damage and its repair by homologous recombination. Proc. Natl. Acad. Sci. USA 2001, 98, 8461–8468.
[16]
Liu, J.; Marians, K.J. Pria-directed assembly of a primosome on d loop DNA. J. Biol. Chem. 1999, 274, 25033–25041, doi:10.1074/jbc.274.35.25033.
[17]
Ng, J.Y.; Marians, K.J. The ordered assembly of the phix174-type primosome. Ii. Preservation of primosome composition from assembly through replication. J. Biol. Chem. 1996, 271, 15649–15655, doi:10.1074/jbc.271.26.15649.
[18]
Liu, J.; Nurse, P.; Marians, K.J. The ordered assembly of the phix174-type primosome. III Prib facilitates complex formation between pria and dnat. J. Biol. Chem. 1996, 271, 15656–15661, doi:10.1074/jbc.271.26.15656.
[19]
Xu, L.; Marians, K.J. Pria mediates DNA replication pathway choice at recombination intermediates. Mol. Cell 2003, 11, 817–826.
[20]
Nurse, P.; Liu, J.; Marians, K.J. Two modes of pria binding to DNA. J. Biol. Chem. 1999, 274, 25026–25032, doi:10.1074/jbc.274.35.25026.
[21]
McGlynn, P.; Al-Deib, A.A.; Liu, J.; Marians, K.J.; Lloyd, R.G. The DNA replication protein pria and the recombination protein recg bind d-loops. J. Mol. Biol. 1997, 270, 212–221, doi:10.1006/jmbi.1997.1120.
[22]
Kowalczykowski, S.C.; Krupp, R.A. Effects of escherichia coli ssb protein on the single-stranded DNA-dependent atpase activity of escherichia coli reca protein. Evidence that ssb protein facilitates the binding of reca protein to regions of secondary structure within single-stranded DNA. J. Mol. Biol. 1987, 193, 97–113, doi:10.1016/0022-2836(87)90630-9.
[23]
Roy, R.; Kozlov, A.G.; Lohman, T.M.; Ha, T. Ssb protein diffusion on single-stranded DNA stimulates reca filament formation. Nature 2009, 461, 1092–1097.
[24]
Umezu, K.; Kolodner, R.D. Protein interactions in genetic recombination in escherichia coli. Interactions involving reco and recr overcome the inhibition of reca by single-stranded DNA-binding protein. J. Biol. Chem. 1994, 269, 30005–30013.
[25]
Umezu, K.; Chi, N.W.; Kolodner, R.D. Biochemical interaction of the escherichia coli recf, reco, and recr proteins with reca protein and single-stranded DNA binding protein. Proc. Natl. Acad. Sci. USA 1993, 90, 3875–3879.
Kuzminov, A.; Stahl, F.W. Double-strand end repair via the recbc pathway in escherichia coli primes DNA replication. Genes Dev. 1999, 13, 345–356, doi:10.1101/gad.13.3.345.
[28]
Dillingham, M.S.; Kowalczykowski, S.C. Recbcd enzyme and the repair of double-stranded DNA breaks. Microbiol. Mol. Biol. Rev. 2008, 72, 642–671, doi:10.1128/MMBR.00020-08.
[29]
Yeeles, J.T.; Dillingham, M.S. The processing of double-stranded DNA breaks for recombinational repair by helicase-nuclease complexes. DNA Repair 2010, 9, 276–285.
[30]
Sakai, A.; Cox, M.M. Recfor and recor as distinct reca loading pathways. J. Biol. Chem. 2009, 284, 3264–3272, doi:10.1074/jbc.M807220200.
[31]
Lovett, S.T.; Kolodner, R.D. Identification and purification of a single-stranded-DNA-specific exonuclease encoded by the recj gene of escherichia coli. Proc. Natl. Acad. Sci. USA 1989, 86, 2627–2631, doi:10.1073/pnas.86.8.2627.
[32]
Umezu, K.; Nakayama, K.; Nakayama, H. Escherichia coli recq protein is a DNA helicase. Proc. Natl. Acad. Sci. USA 1990, 87, 5363–5367, doi:10.1073/pnas.87.14.5363.
[33]
Tseng, Y.C.; Hung, J.L.; Wang, T.C. Involvement of recf pathway recombination genes in postreplication repair in uv-irradiated escherichia coli cells. Mut. Res. 1994, 315, 1–9, doi:10.1016/0921-8777(94)90021-3.
[34]
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. 1999, 262, 543–551, doi:10.1007/s004380051116.
[35]
Webb, B.L.; Cox, M.M.; Inman, R.B. Recombinational DNA repair: The recf and recr proteins limit the extension of reca filaments beyond single-strand DNA gaps. Cell 1997, 91, 347–356.
[36]
Anderson, D.G.; Kowalczykowski, S.C. The translocating recbcd enzyme stimulates recombination by directing reca protein onto ssdna in a chi-regulated manner. Cell 1997, 90, 77–86, doi:10.1016/S0092-8674(00)80315-3.
[37]
Baharoglu, Z.; Petranovic, M.; Flores, M.J.; Michel, B. Ruvab is essential for replication forks reversal in certain replication mutants. EMBO J. 2006, 25, 596–604, doi:10.1038/sj.emboj.7600941.
[38]
Flores, M.J.; Bierne, H.; Ehrlich, S.D.; Michel, B. Impairment of lagging strand synthesis triggers the formation of a ruvabc substrate at replication forks. EMBO J. 2001, 20, 619–629.
[39]
Michel, B.; Ehrlich, S.D.; Uzest, M. DNA double-strand breaks caused by replication arrest. EMBO J. 1997, 16, 430–438, doi:10.1093/emboj/16.2.430.
[40]
Grompone, G.; Seigneur, M.; Ehrlich, S.D.; Michel, B. Replication fork reversal in DNA polymerase III mutants of escherichia coli: A role for the beta clamp. Mol. Microbiol. 2002, 44, 1331–1339, doi:10.1046/j.1365-2958.2002.02962.x.
[41]
Pennington, J.M.; Rosenberg, S.M. Spontaneous DNA breakage in single living escherichia coli cells. Nat. Genet. 2007, 39, 797–802, doi:10.1038/ng2051.
[42]
Seigneur, M.; Bidnenko, V.; Ehrlich, S.D.; Michel, B. Ruvab acts at arrested replication forks. Cell 1998, 95, 419–430.
De Septenville, A.L.; Duigou, S.; Boubakri, H.; Michel, B. Replication fork reversal after replication-transcription collision. PLoS Genet. 2012, 8, doi:10.1371/journal.pgen.1002622.
[45]
Seigneur, M.; Ehrlich, S.D.; Michel, B. Ruvabc-dependent double-strand breaks in dnabts mutants require reca. Mol. Microbiol. 2000, 38, 565–574, doi:10.1046/j.1365-2958.2000.02152.x.
[46]
McGlynn, P.; Lloyd, R.G. Genome stability and the processing of damaged replication forks by recg. Trends Genet. 2002, 18, 413–419.
[47]
McGlynn, P.; Lloyd, R.G.; Marians, K.J. Formation of holliday junctions 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 2001, 98, 8235–8240, doi:10.1073/pnas.121007798.
[48]
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 2001, 98, 8211–8218.
[49]
Flores, M.J.; Bidnenko, V.; Michel, B. The DNA repair helicase uvrd is essential for replication fork reversal in replication mutants. EMBO Rep. 2004, 5, 983–988, doi:10.1038/sj.embor.7400262.
[50]
Flores, M.J.; Sanchez, N.; Michel, B. A fork-clearing role for uvrd. Mol. Microbiol. 2005, 57, 1664–1675.
Koehler, D.R.; Courcelle, J.; Hanawalt, P.C. Kinetics of pyrimidine(6-4)pyrimidone photoproduct repair in escherichia coli. J. Bacteriol. 1996, 178, 1347–1350.
[53]
Howard-Flanders, P.; Boyce, R.P.; Theriot, L. Three loci in escherichia coli k-12 that control the excision of pyrimidine dimers and certain other mutagen products from DNA. Genetics 1966, 53, 1119–1136.
[54]
Howard-Flanders, P.; Theriot, L. Mutants of escherichia coli k-12 defective in DNA repair and in genetic recombination. Genetics 1966, 53, 1137–1150.
[55]
Smith, D.W.; Hanawalt, P.C. Repair replication of DNA in ultraviolet irradiated mycoplasma laidlawii b. J. Mol. Biol. 1969, 46, 57–72, doi:10.1016/0022-2836(69)90057-6.
[56]
Villani, G.; Spadari, S.; Boiteux, S.; Defais, M.; Caillet-Fauquet, P.; Radman, M. Replication of chemically modified DNA. Biochimie 1978, 60, 1145–1150.
[57]
Truglio, J.J.; Karakas, E.; Rhau, B.; Wang, H.; DellaVecchia, M.J.; Van Houten, B.; Kisker, C. Structural basis for DNA recognition and processing by uvrb. Nat. Struct. Mol. Biol. 2006, 13, 360–364.
[58]
Wang, T.C.; Smith, K.C. Mechanisms for recf-dependent and recb-dependent pathways of postreplication repair in uv-irradiated escherichia coli uvrb. J. Bacteriol. 1983, 156, 1093–1098.
[59]
Donaldson, J.R.; Courcelle, C.T.; Courcelle, J. Ruvabc is required to resolve holliday junctions that accumulate following replication on damaged templates in escherichia coli. J. Biol. Chem. 2006, 281, 28811–28821, doi:10.1074/jbc.M603933200.
[60]
Rupp, W.D.; Wilde, C.E., III.; Reno, D.L.; Howard-Flanders, P. Exchanges between DNA strands in ultraviolet-irradiated escherichia coli. J. Mol. Biol. 1971, 61, 25–44, doi:10.1016/0022-2836(71)90204-X.
[61]
Howard-Flanders, P.; Rupp, W.D. Recombinational repair in uv-irradiated escherichia coli. Johns Hopkins Med. J. 1972, 1, 212–225.
[62]
Pages, V.; Fuchs, R.P. Uncoupling of leading- and lagging-strand DNA replication during lesion bypass in vivo. Science 2003, 300, 1300–1303, doi:10.1126/science.1083964.
[63]
Higuchi, K.; Katayama, T.; Iwai, S.; Hidaka, M.; Horiuchi, T.; Maki, H. Fate of DNA replication fork encountering a single DNA lesion during oric plasmid DNA replication in vitro. Genes to Cells: Devoted to Molecular and Cellular Mechanisms 2003, 8, 437–449, doi:10.1046/j.1365-2443.2003.00646.x.
[64]
Yeeles, J.T.; Marians, K.J. The Escherichia coli replisome is inherently DNA damage tolerant. Science 2011, 334, 235–238, doi:10.1126/science.1209111.
[65]
Khidhir, M.A.; Casaregola, S.; Holland, I.B. Mechanism of transient inhibition of DNA synthesis in ultraviolet-irradiated E. coli: Inhibition is independent of reca whilst recovery requires reca protein itself and an additional, inducible sos function. Mol. Gen. Genet. 1985, 199, 133–140, doi:10.1007/BF00327522.
[66]
Courcelle, C.T.; Belle, J.J.; Courcelle, J. Nucleotide excision repair or polymerase v-mediated lesion bypass can act to restore uv-arrested replication forks in escherichia coli. J. Bacteriol. 2005, 187, 6953–6961, doi:10.1128/JB.187.20.6953-6961.2005.
Courcelle, J.; Carswell-Crumpton, C.; Hanawalt, P.C. Recf and recr are required for the resumption of replication at DNA replication forks in escherichia coli. Proc. Natl. Acad. Sci. USA 1997, 94, 3714–3719, doi:10.1073/pnas.94.8.3714.
[70]
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. 1999, 181, 916–922.
[71]
Chow, K.H.; Courcelle, J. Reco acts with recf and recr to protect and maintain replication forks blocked by uv-induced DNA damage in escherichia coli. J. Biol. Chem. 2004, 279, 3492–3496.
[72]
Courcelle, C.T.; Landstrom, A.J.; Anderson, B.; Courcelle, J. Cellular characterization of the primosome and rep helicase in processing and restoration of replication following arrest by uv-induced DNA damage in escherichia coli. J. Bacteriol. 2012, 194, 3977–3986, doi:10.1128/JB.00290-12.
[73]
Hishida, T.; Han, Y.W.; Shibata, T.; Kubota, Y.; Ishino, Y.; Iwasaki, H.; Shinagawa, H. Role of the escherichia coli recq DNA helicase in sos signaling and genome stabilization at stalled replication forks. Genes Dev. 2004, 18, 1886–1897, doi:10.1101/gad.1223804.
[74]
McInerney, P.; O'Donnell, M. Replisome fate upon encountering a leading strand block and clearance from DNA by recombination proteins. J. Biol. Chem. 2007, 282, 25903–25916.
[75]
Courcelle, J.; Hanawalt, P.C. Participation of recombination proteins in rescue of arrested replication forks in uv-irradiated escherichia coli need not involve recombination. Proc. Natl. Acad. Sci. USA 2001, 98, 8196–8202, doi:10.1073/pnas.121008898.
[76]
Courcelle, J.; Ganesan, A.K.; Hanawalt, P.C. Therefore, what are recombination proteins there for? BioEssays 2001, 23, 463–470, doi:10.1002/bies.1065.
[77]
Al-Hadid, Q.; Ona, K.; Courcelle, C.T.; Courcelle, J. Reca433 cells are defective in recf-mediated processing of disrupted replication forks but retain recbcd-mediated functions. Mut. Res. 2008, 645, 19–26.
[78]
Renzette, N.; Gumlaw, N.; Nordman, J.T.; Krieger, M.; Yeh, S.P.; Long, E.; Centore, R.; Boonsombat, R.; Sandler, S.J. Localization of reca in escherichia coli k-12 using reca-gfp. Mol. Microbiol. 2005, 57, 1074–1085, doi:10.1111/j.1365-2958.2005.04755.x.
[79]
Simmons, L.A.; Grossman, A.D.; Walker, G.C. Replication is required for the reca localization response to DNA damage in bacillus subtilis. Proc. Natl. Acad. Sci. USA 2007, 104, 1360–1365.
[80]
Lecointe, F.; Serena, C.; Velten, M.; Costes, A.; McGovern, S.; Meile, J.C.; Errington, J.; Ehrlich, S.D.; Noirot, P.; Polard, P. Anticipating chromosomal replication fork arrest: Ssb targets repair DNA helicases to active forks. EMBO J. 2007, 26, 4239–4251, doi:10.1038/sj.emboj.7601848.
[81]
Costes, A.; Lecointe, F.; McGovern, S.; Quevillon-Cheruel, S.; Polard, P. The c-terminal domain of the bacterial ssb protein acts as a DNA maintenance hub at active chromosome replication forks. PLoS Genet. 2010, 6, doi:10.1371/journal.pgen.1001238.
[82]
Mechali, M. Eukaryotic DNA replication origins: Many choices for appropriate answers. Nat. Rev. Mol. Cell Biol. 2010, 11, 728–738, doi:10.1038/nrm2976.
[83]
Cayrou, C.; Coulombe, P.; Mechali, M. Programming DNA replication origins and chromosome organization. Chrom. Res. 2010, 18, 137–145, doi:10.1007/s10577-009-9105-3.
Szilard, R.; Jacques, P.; Laramée, L.; Cheng, B.; Galicia, S.; Bataille, A.; Yeung, M.; Mendez, M.; Bergeron, M.; Robert, F.; et al. Systematic identification of fragile sites via genome-wide location analysis of gamma-h2ax. Nat. Struct. Mol. Biol. 2010, 17, 299–305, doi:10.1038/nsmb.1754.
[88]
Helleday, T. Homologous recombination in cancer development, treatment and development of drug resistance. Carcinogenesis 2010, 31, 955–960.
[89]
Kawabata, T.; Luebben, S.W.; Yamaguchi, S.; Ilves, I.; Matise, I.; Buske, T.; Botchan, M.R.; Shima, N. Stalled fork rescue via dormant replication origins in unchallenged s phase promotes proper chromosome segregation and tumor suppression. Mol. Cell 2011, 41, 543–553, doi:10.1016/j.molcel.2011.02.006.
[90]
Woodward, A.M.; Gohler, T.; Luciani, M.G.; Oehlmann, M.; Ge, X.; Gartner, A.; Jackson, D.A.; Blow, J.J. Excess mcm2–7 license dormant origins of replication that can be used under conditions of replicative stress. J. Cell Biol. 2006, 173, 673–683, doi:10.1083/jcb.200602108.
[91]
Ge, X.Q.; Jackson, D.A.; Blow, J.J. Dormant origins licensed by excess mcm2–7 are required for human cells to survive replicative stress. Genes Dev. 2007, 21, 3331–3341.
[92]
Le Tallec, B.; Dutrillaux, B.; Lachages, A.M.; Millot, G.A.; Brison, O.; Debatisse, M. Molecular profiling of common fragile sites in human fibroblasts. Nat. Struc. Mol. Biol. 2011, 18, 1421–1423, doi:10.1038/nsmb.2155.
[93]
Letessier, A.; Millot, G.A.; Koundrioukoff, S.; Lachages, A.M.; Vogt, N.; Hansen, R.S.; Malfoy, B.; Brison, O.; Debatisse, M. Cell-type-specific replication initiation programs set fragility of the fra3b fragile site. Nature 2011, 470, 120–123.
[94]
Daboussi, F.; Courbet, S.; Benhamou, S.; Kannouche, P.; Zdzienicka, M.Z.; Debatisse, M.; Lopez, B.S. A homologous recombination defect affects replication-fork progression in mammalian cells. J. Cell Sci. 2008, 121, 162–166.
[95]
Branzei, D.; Foiani, M. Maintaining genome stability at the replication fork. Nat. Rev. Mol. Cell Biol. 2010, 11, 208–219, doi:10.1038/nrm2852.
[96]
Katou, Y.; Kanoh, Y.; Bando, M.; Noguchi, H.; Tanaka, H.; Ashikari, T.; Sugimoto, K.; Shirahige, K. S-phase checkpoint proteins tof1 and mrc1 form a stable replication-pausing complex. Nature 2003, 424, 1078–1083, doi:10.1038/nature01900.
[97]
De Piccoli, G.; Katou, Y.; Itoh, T.; Nakato, R.; Shirahige, K.; Labib, K. Replisome stability at defective DNA replication forks is independent of s phase checkpoint kinases. Mol. Cell 2012, 45, 696–704.
[98]
Cotta-Ramusino, C.; Fachinetti, D.; Lucca, C.; Doksani, Y.; Lopes, M.; Sogo, J.; Foiani, M. Exo1 processes stalled replication forks and counteracts fork reversal in checkpoint-defective cells. Mol. Cell 2005, 17, 153–159, doi:10.1016/j.molcel.2004.11.032.
[99]
Froget, B.; Blaisonneau, J.; Lambert, S.; Baldacci, G. Cleavage of stalled forks by fission yeast mus81/eme1 in absence of DNA replication checkpoint. Mol. Biol.Cell 2008, 19, 445–456.
[100]
Kai, M.; Boddy, M.N.; Russell, P.; Wang, T.S. Replication checkpoint kinase cds1 regulates mus81 to preserve genome integrity during replication stress. Genes Dev. 2005, 19, 919–932, doi:10.1101/gad.1304305.
[101]
Hu, J.; Sun, L.; Shen, F.; Chen, Y.; Hua, Y.; Liu, Y.; Zhang, M.; Hu, Y.; Wang, Q.; Xu, W.; et al. The intra-s phase checkpoint targets dna2 to prevent stalled replication forks from reversing. Cell 2012, 149, 1221–1232.
[102]
Nimonkar, A.V.; Sica, R.A.; Kowalczykowski, S.C. Rad52 promotes second-end DNA capture in double-stranded break repair to form complement-stabilized joint molecules. Proc. Natl. Acad. Sci. USA 2009, 106, 3077–3082.
[103]
McIlwraith, M.J.; West, S.C. DNA repair synthesis facilitates rad52-mediated second-end capture during dsb repair. Mol. Cell 2008, 29, 510–516, doi:10.1016/j.molcel.2007.11.037.
[104]
Carreira, A.; Hilario, J.; Amitani, I.; Baskin, R.J.; Shivji, M.K.; Venkitaraman, A.R.; Kowalczykowski, S.C. The brc repeats of brca2 modulate the DNA-binding selectivity of rad51. Cell 2009, 136, 1032–1043, doi:10.1016/j.cell.2009.02.019.
Wray, J.; Liu, J.; Nickoloff, J.A.; Shen, Z. Distinct rad51 associations with rad52 and bccip in response to DNA damage and replication stress. Cancer Res. 2008, 68, 2699–2707, doi:10.1158/0008-5472.CAN-07-6505.
[107]
Lisby, M.; Barlow, J.H.; Burgess, R.C.; Rothstein, R. Choreography of the DNA damage response: Spatiotemporal relationships among checkpoint and repair proteins. Cell 2004, 118, 699–713, doi:10.1016/j.cell.2004.08.015.
[108]
Sung, P. Yeast rad55 and rad57 proteins form a heterodimer that functions with replication protein a to promote DNA strand exchange by rad51 recombinase. Genes Dev. 1997, 11, 1111–1121.
[109]
Ward, J.D.; Barber, L.J.; Petalcorin, M.I.; Yanowitz, J.; Boulton, S.J. Replication blocking lesions present a unique substrate for homologous recombination. EMBO J. 2007, 26, 3384–3396, doi:10.1038/sj.emboj.7601766.
[110]
Mankouri, H.W.; Ngo, H.P.; Hickson, I.D. Shu proteins promote the formation of homologous recombination intermediates that are processed by sgs1-rmi1-top3. Mol. Biol Cell 2007, 18, 4062–4073.
[111]
Shor, E.; Weinstein, J.; Rothstein, R. A genetic screen for top3 suppressors in saccharomyces cerevisiae identifies shu1, shu2, psy3 and csm2: Four genes involved in error-free DNA repair. Genetics 2005, 169, 1275–1289.
[112]
Ball, L.G.; Zhang, K.; Cobb, J.A.; Boone, C.; Xiao, W. The yeast shu complex couples error-free post-replication repair to homologous recombination. Mol. Microbiol. 2009, 73, 89–102, doi:10.1111/j.1365-2958.2009.06748.x.
[113]
Choi, K.; Szakal, B.; Chen, Y.H.; Branzei, D.; Zhao, X. The smc5/6 complex and esc2 influence multiple replication-associated recombination processes in saccharomyces cerevisiae. Mol. Biol Cell 2010, 21, 2306–2314, doi:10.1091/mbc.E10-01-0050.
[114]
Martin, V.; Chahwan, C.; Gao, H.; Blais, V.; Wohlschlegel, J.; Yates, J.R., III.; McGowan, C.H.; Russell, P. Sws1 is a conserved regulator of homologous recombination in eukaryotic cells. EMBO J. 2006, 25, 2564–2574, doi:10.1038/sj.emboj.7601141.
Papouli, E.; Chen, S.; Davies, A.A.; Huttner, D.; Krejci, L.; Sung, P.; Ulrich, H.D. Crosstalk between sumo and ubiquitin on pcna is mediated by recruitment of the helicase srs2p. Mol. Cell 2005, 19, 123–133, doi:10.1016/j.molcel.2005.06.001.
[117]
Pfander, B.; Moldovan, G.L.; Sacher, M.; Hoege, C.; Jentsch, S. Sumo-modified pcna recruits srs2 to prevent recombination during s phase. Nature 2005, 436, 428–433.
[118]
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. 2000, 20, 4393–4404, doi:10.1128/MCB.20.12.4393-4404.2000.
[119]
Herzberg, K.; Bashkirov, V.I.; Rolfsmeier, M.; Haghnazari, E.; McDonald, W.H.; Anderson, S.; Bashkirova, E.V.; Yates, J.R., III.; Heyer, W.D. 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. 2006, 26, 8396–8409.
[120]
Haaf, T.; Golub, E.I.; Reddy, G.; Radding, C.M.; Ward, D.C. Nuclear foci of mammalian rad51 recombination protein in somatic cells after DNA damage and its localization in synaptonemal complexes. Proc. Natl. Acad. Sci. USA 1995, 92, 2298–2302.
[121]
Tashiro, S.; Kotomura, N.; Shinohara, A.; Tanaka, K.; Ueda, K.; Kamada, N. S phase specific formation of the human rad51 protein nuclear foci in lymphocytes. Oncogene 1996, 12, 2165–2170.
[122]
Golub, E.I.; Gupta, R.C.; Haaf, T.; Wold, M.S.; Radding, C.M. Interaction of human rad51 recombination protein with single-stranded DNA binding protein, rpa. Nucleic Acids Res. 1998, 26, 5388–5393, doi:10.1093/nar/26.23.5388.
[123]
Raderschall, E.; Golub, E.I.; Haaf, T. Nuclear foci of mammalian recombination proteins are located at single-stranded DNA regions formed after DNA damage. Proc. Natl. Acad. Sci. USA 1999, 96, 1921–1926, doi:10.1073/pnas.96.5.1921.
[124]
Mizuta, R.; LaSalle, J.M.; Cheng, H.L.; Shinohara, A.; Ogawa, H.; Copeland, N.; Jenkins, N.A.; Lalande, M.; Alt, F.W. Rab22 and rab163/mouse brca2: Proteins that specifically interact with the rad51 protein. Proc. Natl. Acad. Sci. USA 1997, 94, 6927–6932.
[125]
Tashiro, S.; Walter, J.; Shinohara, A.; Kamada, N.; Cremer, T. Rad51 accumulation at sites of DNA damage and in postreplicative chromatin. J. Cell Biol. 2000, 150, 283–291, doi:10.1083/jcb.150.2.283.
[126]
Chen, J.; Silver, D.P.; Walpita, D.; Cantor, S.B.; Gazdar, A.F.; Tomlinson, G.; Couch, F.J.; Weber, B.L.; Ashley, T.; Livingston, D.M.; et al. Stable interaction between the products of the brca1 and brca2 tumor suppressor genes in mitotic and meiotic cells. Mol. Cell 1998, 2, 317–328, doi:10.1016/S1097-2765(00)80276-2.
[127]
Scully, R.; Chen, J.; Plug, A.; Xiao, Y.; Weaver, D.; Feunteun, J.; Ashley, T.; Livingston, D.M. Association of brca1 with rad51 in mitotic and meiotic cells. Cell 1997, 88, 265–275.
[128]
Scully, R.; Chen, J.; Ochs, R.L.; Keegan, K.; Hoekstra, M.; Feunteun, J.; Livingston, D.M. Dynamic changes of brca1 subnuclear location and phosphorylation state are initiated by DNA damage. Cell 1997, 90, 425–435, doi:10.1016/S0092-8674(00)80503-6.
[129]
Meister, P.; Poidevin, M.; Francesconi, S.; Tratner, I.; Zarzov, P.; Baldacci, G. Nuclear factories for signalling and repairing DNA double strand breaks in living fission yeast. Nucleic Acids Res. 2003, 31, 5064–5073, doi:10.1093/nar/gkg719.
[130]
Lisby, M.; Rothstein, R.; Mortensen, U.H. Rad52 forms DNA repair and recombination centers during s phase. Proc. Natl. Acad. Sci. USA 2001, 98, 8276–8282.
[131]
Lambert, S.; Mizuno, K.; Blaisonneau, J.; Martineau, S.; Chanet, R.; Fréon, K.; Murray, J.M.; Carr, A.M.; Baldacci, G. Homologous recombination restarts blocked replication forks at the expense of genome rearrangements by template exchange. Mol. Cell 2010, 39, 346–359, doi:10.1016/j.molcel.2010.07.015.
[132]
Lambert, S.; Watson, A.; Sheedy, D.M.; Martin, B.; Carr, A.M. Gross chromosomal rearrangements and elevated recombination at an inducible site-specific replication fork barrier. Cell 2005, 121, 689–702, doi:10.1016/j.cell.2005.03.022.
[133]
Mizuno, K.; Lambert, S.; Baldacci, G.; Murray, J.M.; Carr, A.M. Nearby inverted repeats fuse to generate acentric and dicentric palindromic chromosomes by a replication template exchange mechanism. Genes Dev. 2009, 23, 2876–2886, doi:10.1101/gad.1863009.
[134]
Zou, H.; Rothstein, R. Holliday junctions accumulate in replication mutants via a reca homolog-independent mechanism. Cell 1997, 90, 87–96.
[135]
Tsang, E.; Carr, A. Replication fork arrest, recombination and the maintenance of ribosomal DNA stability. DNA Repair 2008, 7, 1613–1623, doi:10.1016/j.dnarep.2008.06.010.
[136]
Karanam, K.; Kafri, R.; Loewer, A.; Lahav, G. Quantitative live cell imaging reveals a gradual shift between DNA repair mechanisms and a maximal use of hr in mid s phase. Mol. Cell 2012, 47, 320–329.
[137]
Wong, J.M.; Ionescu, D.; Ingles, C.J. Interaction between brca2 and replication protein a is compromised by a cancer-predisposing mutation in brca2. Oncogene 2003, 22, 28–33, doi:10.1038/sj.onc.1206071.
[138]
Shukla, A.; Navadgi, V.M.; Mallikarjuna, K.; Rao, B.J. Interaction of hrad51 and hrad52 with mcm complex: A cross-talk between recombination and replication proteins. Biochem. Biophys. Res. Commun. 2005, 329, 1240–1245, doi:10.1016/j.bbrc.2005.02.106.
[139]
Bailis, J.M.; Luche, D.D.; Hunter, T.; Forsburg, S.L. Minichromosome maintenance proteins interact with checkpoint and recombination proteins to promote s-phase genome stability. Mol. Cell. Biol. 2008, 28, 1724–1738, doi:10.1128/MCB.01717-07.
[140]
Oyola, S.O.; Bringaud, F.; Melville, S.E. A kinetoplastid brca2 interacts with DNA replication protein cdc45. Int. J. Parasitol. 2009, 39, 59–69.
[141]
Alabert, C.; Bianco, J.; Pasero, P. Differential regulation of homologous recombination at DNA breaks and replication forks by the mrc1 branch of the s-phase checkpoint. EMBO J. 2009, 28, 1131–1141, doi:10.1038/emboj.2009.75.
[142]
Lopes, M.; Foiani, M.; Sogo, J.M. Multiple mechanisms control chromosome integrity after replication fork uncoupling and restart at irreparable uv lesions. Mol. Cell 2006, 21, 15–27, doi:10.1016/j.molcel.2005.11.015.
[143]
Hashimoto, Y.; Ray Chaudhuri, A.; Lopes, M.; Costanzo, V. Rad51 protects nascent DNA from mre11-dependent degradation and promotes continuous DNA synthesis. Nat. Struc. Mol. Biol. 2010, 17, 1305–1311, doi:10.1038/nsmb.1927.
[144]
Liberi, G.; Maffioletti, G.; Lucca, C.; Chiolo, I.; Baryshnikova, A.; Cotta-Ramusino, C.; Lopes, M.; Pellicioli, A.; Haber, J.E.; Foiani, M. Rad51-dependent DNA structures accumulate at damaged replication forks in sgs1 mutants defective in the yeast ortholog of blm recq helicase. Genes Dev. 2005, 19, 339–350.
Branzei, D.; Sollier, J.; Liberi, G.; Zhao, X.; Maeda, D.; Seki, M.; Enomoto, T.; Ohta, K.; Foiani, M. Ubc9- and mms21-mediated sumoylation counteracts recombinogenic events at damaged replication forks. Cell 2006, 127, 509–522, doi:10.1016/j.cell.2006.08.050.
[147]
Mankouri, H.W.; Ashton, T.M.; Hickson, I.D. Holliday junction-containing DNA structures persist in cells lacking sgs1 or top3 following exposure to DNA damage. Proc. Nat. Acad. Sci. USA 2011, 108, 4944–4949, doi:10.1073/pnas.1014240108.
[148]
Branzei, D. Ubiquitin family modifications and template switching. FEBS Lett. 2011, 585, 2810–2817.
[149]
Vanoli, F.; Fumasoni, M.; Szakal, B.; Maloisel, L.; Branzei, D. Replication and recombination factors contributing to recombination-dependent bypass of DNA lesions by template switch. PLoS Genet. 2010, 6, doi:10.1371/journal.pgen.1001205.
[150]
Moriel-Carretero, M.; Aguilera, A. A postincision-deficient tfiih causes replication fork breakage and uncovers alternative rad51- or pol32-mediated restart mechanisms. Mol. Cell 2010, 37, 690–701, doi:10.1016/j.molcel.2010.02.008.
[151]
Roseaulin, L.; Yamada, Y.; Tsutsui, Y.; Russell, P.; Iwasaki, H.; Arcangioli, B. Mus81 is essential for sister chromatid recombination at broken replication forks. EMBO J. 2008, 27, 1378–1387, doi:10.1038/emboj.2008.65.
[152]
Hashimoto, Y.; Puddu, F.; Costanzo, V. Rad51- and mre11-dependent reassembly of uncoupled cmg helicase complex at collapsed replication forks. Nat. Struc. Mol. Biol. 2011, 19, 17–24, doi:10.1038/nsmb.2177.
[153]
Clemente-Ruiz, M.; Prado, F. Chromatin assembly controls replication fork stability. EMBO Rep. 2009, 10, 790–796.
[154]
Long, D.T.; Raschle, M.; Joukov, V.; Walter, J.C. Mechanism of rad51-dependent DNA interstrand cross-link repair. Science 2011, 333, 84–87.
[155]
Bjergbaek, L.; Cobb, J.A.; Tsai-Pflugfelder, M.; Gasser, S.M. Mechanistically distinct roles for sgs1p in checkpoint activation and replication fork maintenance. EMBO J. 2005, 24, 405–417, doi:10.1038/sj.emboj.7600511.
[156]
Nakahara, M.; Sonoda, E.; Nojima, K.; Sale, J.E.; Takenaka, K.; Kikuchi, K.; Taniguchi, Y.; Nakamura, K.; Sumitomo, Y.; Bree, R.T.; et al. Genetic evidence for single-strand lesions initiating nbs1-dependent homologous recombination in diversification of ig v in chicken b lymphocytes. PLoS Genet. 2009, 5, doi:10.1371/journal.pgen.1000356.
[157]
Paek, A.L.; Kaochar, S.; Jones, H.; Elezaby, A.; Shanks, L.; Weinert, T. Fusion of nearby inverted repeats by a replication-based mechanism leads to formation of dicentric and acentric chromosomes that cause genome instability in budding yeast. Genes Dev. 2009, 23, 2861–2875.
[158]
Meister, P.; Taddei, A.; Vernis, L.; Poidevin, M.; Gasser, S.M.; Baldacci, G. Temporal separation of replication and recombination requires the intra-s checkpoint. J. Cell Biol. 2005, 168, 537–544, doi:10.1083/jcb.200410006.
[159]
Sorensen, C.S.; Hansen, L.T.; Dziegielewski, J.; Syljuasen, R.G.; Lundin, C.; Bartek, J.; Helleday, T. The cell-cycle checkpoint kinase chk1 is required for mammalian homologous recombination repair. Nat. Cell Biol. 2005, 7, 195–201, doi:10.1038/ncb1212.
[160]
Petermann, E.; Orta, M.L.; Issaeva, N.; Schultz, N.; Helleday, T. Hydroxyurea-stalled replication forks become progressively inactivated and require two different rad51-mediated pathways for restart and repair. Mol. Cell 2010, 37, 492–502, doi:10.1016/j.molcel.2010.01.021.
[161]
Saintigny, Y.; Delacote, F.; Vares, G.; Petitot, F.; Lambert, S.; Averbeck, D.; Lopez, B.S. Characterization of homologous recombination induced by replication inhibition in mammalian cells. EMBO J. 2001, 20, 3861–3870.
[162]
Raveendranathan, M.; Chattopadhyay, S.; Bolon, Y.T.; Haworth, J.; Clarke, D.J.; Bielinsky, A.K. Genome-wide replication profiles of s-phase checkpoint mutants reveal fragile sites in yeast. EMBO J. 2006, 25, 3627–3639, doi:10.1038/sj.emboj.7601251.
[163]
Hanada, K.; Budzowska, M.; Davies, S.L.; van Drunen, E.; Onizawa, H.; Beverloo, H.B.; Maas, A.; Essers, J.; Hickson, I.D.; Kanaar, R. The structure-specific endonuclease mus81 contributes to replication restart by generating double-strand DNA breaks. Nat. Struc. Mol. Biol. 2007, 14, 1096–1104, doi:10.1038/nsmb1313.
[164]
Bosco, G.; Haber, J.E. Chromosome break-induced DNA replication leads to nonreciprocal translocations and telomere capture. Genetics 1998, 150, 1037–1047.
[165]
Llorente, B.; Smith, C.E.; Symington, L.S. Break-induced replication: What is it and what is it for? Cell Cycle 2008, 7, 859–864.
[166]
Kraus, E.; Leung, W.Y.; Haber, J.E. Break-induced replication: A review and an example in budding yeast. Proc. Natl. Acad. Sci. USA 2001, 98, 8255–8262, doi:10.1073/pnas.151008198.
Stracker, T.H.; Petrini, J.H. The mre11 complex: Starting from the ends. Nat. Rev. Mol. Cell Biol. 2011, 12, 90–103, doi:10.1038/nrm3047.
[173]
Lomonosov, M.; Anand, S.; Sangrithi, M.; Davies, R.; Venkitaraman, A.R. Stabilization of stalled DNA replication forks by the brca2 breast cancer susceptibility protein. Genes Dev. 2003, 17, 3017–3022, doi:10.1101/gad.279003.
[174]
Schlacher, K.; Christ, N.; Siaud, N.; Egashira, A.; Wu, H.; Jasin, M. Double-strand break repair-independent role for brca2 in blocking stalled replication fork degradation by mre11. Cell 2011, 145, 529–542, doi:10.1016/j.cell.2011.03.041.
[175]
Schlacher, K.; Wu, H.; Jasin, M. A distinct replication fork protection pathway connects fanconi anemia tumor suppressors to rad51-brca1/2. Cancer Cell 2012, 22, 106–116.
[176]
Tinline-Purvis, H.; Savory, A.P.; Cullen, J.K.; Dave, A.; Moss, J.; Bridge, W.L.; Marguerat, S.; Bahler, J.; Ragoussis, J.; Mott, R.; et al. Failed gene conversion leads to extensive end processing and chromosomal rearrangements in fission yeast. EMBO J. 2009, 28, 3400–3412, doi:10.1038/emboj.2009.265.
[177]
Sonoda, E.; Sasaki, M.S.; Buerstedde, J.M.; Bezzubova, O.; Shinohara, A.; Ogawa, H.; Takata, M.; Yamaguchi-Iwai, Y.; Takeda, S. Rad51-deficient vertebrate cells accumulate chromosomal breaks prior to cell death. EMBO J. 1998, 17, 598–608, doi:10.1093/emboj/17.2.598.
[178]
Venkitaraman, A.R. Chromosome stability, DNA recombination and the brca2 tumour suppressor. Curr. Opin. Cell Biol. 2001, 13, 338–343, doi:10.1016/S0955-0674(00)00217-9.
[179]
Fachinetti, D.; Bermejo, R.; Cocito, A.; Minardi, S.; Katou, Y.; Kanoh, Y.; Shirahige, K.; Azvolinsky, A.; Zakian, V.A.; Foiani, M. Replication termination at eukaryotic chromosomes is mediated by top2 and occurs at genomic loci containing pausing elements. Mol. Cell 2010, 39, 595–605.
[180]
Nitiss, J. DNA topoisomerase ii and its growing repertoire of biological functions. Natl. Rev. Cancer 2009, 9, 327–337, doi:10.1038/nrc2608.
[181]
Steinacher, R.; Osman, F.; Dalgaard, J.Z.; Lorenz, A.; Whitby, M.C. The DNA helicase pfh1 promotes fork merging at replication termination sites to ensure genome stability. Genes Dev. 2012, 26, 594–602, doi:10.1101/gad.184663.111.
[182]
Kojic, M.; Holloman, W.K. Brh2 domain function distinguished by differential cellular responses to DNA damage and replication stress. Mol. Microbiol. 2012, 83, 351–361.
[183]
Heyer, W.D.; Li, X.; Rolfsmeier, M.; Zhang, X.P. Rad54: The swiss army knife of homologous recombination? Nucleic Acids Res. 2006, 34, 4115–4125, doi:10.1093/nar/gkl481.
[184]
Lambert, S.; Lopez, B.S. Characterization of mammalian rad51 double strand break repair using non-lethal dominant-negative forms. EMBO J. 2000, 19, 3090–3099, doi:10.1093/emboj/19.12.3090.
[185]
Liu, P.; Carvalho, C.M.; Hastings, P.; Lupski, J.R. Mechanisms for recurrent and complex human genomic rearrangements. Curr. Opin. Genet. Dev. 2012, 22, 211–220, doi:10.1016/j.gde.2012.02.012.
[186]
Halazonetis, T.D.; Gorgoulis, V.G.; Bartek, J. An oncogene-induced DNA damage model for cancer development. Science 2008, 319, 1352–1355, doi:10.1126/science.1140735.
[187]
Chabosseau, P.; Buhagiar-Labarchede, G.; Onclercq-Delic, R.; Lambert, S.; Debatisse, M.; Brison, O.; Amor-Gueret, M. Pyrimidine pool imbalance induced by blm helicase deficiency contributes to genetic instability in bloom syndrome. Natl. Commun. 2011, 2, 368.
[188]
Bester, A.C.; Roniger, M.; Oren, Y.S.; Im, M.M.; Sarni, D.; Chaoat, M.; Bensimon, A.; Zamir, G.; Shewach, D.S.; Kerem, B. Nucleotide deficiency promotes genomic instability in early stages of cancer development. Cell 2011, 145, 435–446, doi:10.1016/j.cell.2011.03.044.
[189]
Evers, B.; Helleday, T.; Jonkers, J. Targeting homologous recombination repair defects in cancer. Trends Pharmacol. Sci. 2010, 31, 372–380, doi:10.1016/j.tips.2010.06.001.
