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Multiple mechanisms of repairing meganuclease-induced double-strand DNA breaks in budding yeast

  • Chapter
Molecular Genetics of Recombination

Part of the book series: Topics in Current Genetics ((TCG,volume 17))

Abstract

Double-strand breaks (DSBs) threaten the integrity of chromosomes. Consequently, cells have devised a number of mechanisms to repair broken chromosomes. There are several competing mechanisms of homologous recombination as well as multiple nonhomologous end-joining pathways that can repair chromosome breaks with varying degrees of fidelity. This review summarizes what has been learned about DSB repair in the budding yeast, Saccharomyces cerevisiae, where it is possible to create, rapidly and synchronously, a specific DSB using inducible meganucleases, HO or I-SceI. The physical monitoring of DNA undergoing recombination and the binding of various recombination proteins in the vicinity of the DSB provides a picture of the sequence of molecular events during recombination. We first examine an intrachromosomal recombination event, MAT gene switching, and then to interchromosomal ectopic events. In addition, repair by single-stand annealing, break-induced replication and nonhomologous end-joining are discussed.

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References

  • Aylon Y, Liefshitz B, Kupiec M (2004) The CDK regulates repair of double-strand breaks by homologous recombination during the cell cycle. EMBO J 23:4868–4875

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bai Y, Symington LS (1996) A RAD52 homolog is required for RAD51-independent mitotic recombination in Saccharomyces cerevisiae. Genes Dev 10:2025–2037

    CAS  PubMed  Google Scholar 

  • Bibikova M, Carroll D, Segal DJ, Trautman JK, Smith J, Kim YG, Chandrasegaran S (2001) Stimulation of homologous recombination through targeted cleavage by chimeric nucleases. Mol Cell Biol 21:289–297

    CAS  PubMed Central  PubMed  Google Scholar 

  • Borts RH, Lichten M, Hearn M, Davidow LS, Haber JE (1984) Physical monitoring of meiotic recombination in Saccharomyces cerevisiae. Cold Spring Harb Symp Quant Biol 49:67–76

    CAS  PubMed  Google Scholar 

  • Bosco G, Haber JE (1998) Chromosome break-induced DNA replication leads to nonreciprocal translocations and telomere capture. Genetics 150:1037–1047

    CAS  PubMed Central  PubMed  Google Scholar 

  • Boulton SJ, Jackson SP (1996) Saccharomyces cerevisiae Ku70 potentiates illegitimate DNA double-strand break repair and serves as a barrier to error-prone DNA repair pathways. EMBO J 15:5093–5103

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bressan DA, Vazquez J, Haber JE (2004) Mating type-dependent constraints on the mobility of the left arm of yeast chromosome III. J Cell Biol 164:361–371

    CAS  PubMed Central  PubMed  Google Scholar 

  • Callebaut I, Malivert L, Fischer A, Mornon JP, Revy P, de Villartay JP (2006) Cernunnos interacts with the XRCC4 x DNA-ligase IV complex and is homologous to the yeast nonhomologous end-joining factor Nej1. J Biol Chem 281:13857–13860

    CAS  PubMed  Google Scholar 

  • Chai B, Huang J, Cairns BR, Laurent BC (2005) Distinct roles for the RSC and Swi/Snf ATP-dependent chromatin remodelers in DNA double-strand break repair. Genes Dev 19:1656–1661

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chen Q, IJpma A, Greider CW (2001) Two survivor pathways that allow growth in the absence of telomerase are generated by distinct telomere recombination events. Mol Cell Biol 21:1819–1827

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chen W, Jinks-Robertson S (1998) Mismatch repair proteins regulate heteroduplex formation during mitotic recombination in yeast. Mol Cell Biol 18:6525–6537

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cho JW, Khalsa GJ, Nickoloff JA (1998) Gene-conversion tract directionality is influenced by the chromosome environment. Curr Genet 34:269–279

    CAS  PubMed  Google Scholar 

  • Cohen H, Sinclair DA (2001) Recombination-mediated lengthening of terminal telomeric repeats requires the Sgs1 DNA helicase. Proc Natl Acad Sci USA 98:3174–3179

    CAS  PubMed Central  PubMed  Google Scholar 

  • Colaiácovo MP, Pâques F, Haber JE (1999) Removal of one nonhomologous DNA end during gene conversion by a RAD1-and MSH2-independent pathway. Genetics 151:1409–1423

    PubMed Central  PubMed  Google Scholar 

  • Cromie GA, Leach DR (2000) Control of crossing over. Mol Cell 6:815–826

    CAS  PubMed  Google Scholar 

  • Daley JM, Palmbos PL, Wu D, Wilson TE (2005) Nonhomologous end joining in yeast. Annu Rev Genet 39:431–451

    CAS  PubMed  Google Scholar 

  • Daley JM, Wilson TE (2005) Rejoining of DNA double-strand breaks as a function of overhang length. Mol Cell Biol 25:896–906

    CAS  PubMed Central  PubMed  Google Scholar 

  • Davis AP, Symington LS (2004) RAD51-dependent break-induced replication in yeast. Mol Cell Biol 24:2344–2351

    CAS  PubMed Central  PubMed  Google Scholar 

  • de los Santos T, Hunter N, Lee C, Larkin B, Loidl J, Hollingsworth NM (2003) The Mus81/Mms4 endonuclease acts independently of double-Holliday junction resolution to promote a distinct subset of crossovers during meiosis in budding yeast. Genetics 164:81–94

    PubMed Central  PubMed  Google Scholar 

  • Dunn B, Szauter P, Pardue ML, Szostak JW (1984) Transfer of yeast telomeres to linear plasmids by recombination. Cell 39:191–201

    CAS  PubMed  Google Scholar 

  • Eggler AL, Inman RB, Cox MM (2002) The Rad51-dependent pairing of long DNA substrates is stabilized by replication protein A. J Biol Chem 277:39280–39288

    CAS  PubMed  Google Scholar 

  • Elliott B, Richardson C, Winderbaum J, Nickoloff JA, Jasin M (1998) Gene conversion tracts from double-strand break repair in mammalian cells. Mol Cell Biol 18:93–101

    CAS  PubMed Central  PubMed  Google Scholar 

  • Esposito MS (1978) Evidence that spontaneous mitotic recombination occurs at the two-strand stage. Proc Natl Acad Sci USA 75:4436–4440

    CAS  PubMed Central  PubMed  Google Scholar 

  • Esposito MS, Ramirez RM, Bruschi CV (1994) Nonrandomly-associated forward mutation and mitotic recombination yield yeast diploids homozygous for recessive mutations. Curr Genet 26:302–307

    CAS  PubMed  Google Scholar 

  • Fishman-Lobell J, Haber JE (1992) Removal of nonhomologous DNA ends in double-strand break recombination: the role of the yeast ultraviolet repair gene RAD1. Science 258:480–484

    CAS  PubMed  Google Scholar 

  • Fishman-Lobell J, Rudin N, Haber JE (1992) Two alternative pathways of double-strand break repair that are kinetically separable and independently modulated. Mol Cell Biol 12:1292–1303

    CAS  PubMed Central  PubMed  Google Scholar 

  • Frank-Vaillant M, Marcand S (2001) NHEJ regulation by mating type is exercised through a novel protein, Lif2p, essential to the ligase IV pathway. Genes Dev 15:3005–3012

    CAS  PubMed Central  PubMed  Google Scholar 

  • Frank-Vaillant M, Marcand S (2002) Transient stability of DNA ends allows nonhomolo-gous end joining to precede homologous recombination. Mol Cell 10:1189–1199

    CAS  PubMed  Google Scholar 

  • Gloor GB, Nassif NA, Johnson-Schlitz DM, Preston CR, Engels WR (1991) Targeted gene replacement in Drosophila via P element-induced gap repair. Science 253:1110–1117

    CAS  PubMed  Google Scholar 

  • Golub EI, Gupta RC, Haaf T, Wold MS, Radding CM (1998) Interaction of human rad51 recombination protein with single-stranded DNA binding protein, RPA. Nucleic Acids Res 26:5388–5393

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gould SJ (1997) The exaptive excellence of spandrels as a term and prototype. Proc Natl Acad Sci USA 94:10750–10755

    CAS  PubMed Central  PubMed  Google Scholar 

  • Grandin N, Charbonneau M (2003) Mitotic cyclins regulate telomeric recombination in telomerase-deficient yeast cells. Mol Cell Biol 23:9162–9177

    CAS  PubMed Central  PubMed  Google Scholar 

  • Griffith JD, Comeau L, Rosenfield S, Stansel RM, Bianchi A, Moss H, de Lange T (1999) Mammalian telomeres end in a large duplex loop [see comments]. Cell 97:503–514

    CAS  PubMed  Google Scholar 

  • Guirouilh-Barbat J, Huck S, Bertrand P, Pirzio L, Desmaze C, Sabatier L, Lopez BS (2004) Impact of the KU80 pathway on NHEJ-induced genome rearrangements in mammalian cells. Mol Cell 14:611–623

    CAS  PubMed  Google Scholar 

  • Haber JE, Ray BL, Kolb JM, White CI (1993) Rapid kinetics of mismatch repair of hetero-duplex DNA that is formed during recombination in yeast. Proc Natl Acad Sci USA 90:3363–3367

    CAS  PubMed Central  PubMed  Google Scholar 

  • Haber JE, Leung WY (1996) Lack of chromosome territoriality in yeast: promiscuous re-joining of broken chromosome ends. Proc Natl Acad Sci USA 93:13949–13954

    CAS  PubMed Central  PubMed  Google Scholar 

  • Holmes A, Haber JE (1999) Double-strand break repair in yeast requires both leading and lagging strand DNA polymerases. Cell 96:415–424

    CAS  PubMed  Google Scholar 

  • Horowitz H, Haber JE (1985) Identification of autonomously replicating circular subtelomeric Y’ elements in Saccharomyces cerevisiae. Mol Cell Biol 5:2369–2380

    CAS  PubMed Central  PubMed  Google Scholar 

  • Huang P, Pryde FE, Lester D, Maddison RL, Borts RH, Hickson ID, Louis EJ (2001) SGS1 is required for telomere elongation in the absence of telomerase. Curr Biol 11:125–129

    CAS  PubMed  Google Scholar 

  • Inbar O, Kupiec M (1999) Homology search and choice of homologous partner during mitotic recombination. Mol Cell Biol 19:4134–4142

    CAS  PubMed Central  PubMed  Google Scholar 

  • Inbar O, Liefshitz B, Bitan G, Kupiec M (2000) The relationship between homology length and crossing-over during the repair of a broken chromosome. J Biol Chem 275:30833–30838

    CAS  PubMed  Google Scholar 

  • Ira G, Haber JE (2002) Characterization of RAD51-independent break-induced replication that acts preferentially with short homologous sequences. Mol Cell Biol 22:6384–6392

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ira G, Malkova A, Liberi G, Foiani M, Haber JE (2003) Srs2 and Sgs1-Top3 suppress crossovers during double-strand break repair in yeast. Cell 115:401–411

    CAS  PubMed  Google Scholar 

  • Ira G, Pellicioli A, Balijja A, Wang X, Fiorani S, Carotenuto W, Liberi G, Bressan D, Wan L, Hollingsworth NM, Haber JE, Foiani M (2004) DNA end resection, homologous re-combination and DNA damage checkpoint activation require CDK1. Nature 431:1011–1017

    CAS  PubMed  Google Scholar 

  • Ivanov EL, Sugawara N, White CI, Fabre F, Haber JE (1994) Mutations in XRS2 and RAD50 delay but do not prevent mating-type switching in Saccharomyces cerevisiae. Mol Cell Biol 14:3414–3425

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ivanov EL, Haber JE (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

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ivanov EL, Sugawara N, Fishman LJ, Haber JE (1996) Genetic requirements for the single-strand annealing pathway of double-strand break repair in Saccharomyces cerevisiae. Genetics 142:693–704

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jensen RE, Herskowitz I (1984) Directionality and regulation of cassette substitution in yeast. Cold Spring Harb Symp Quant Biol 49:97–104

    CAS  PubMed  Google Scholar 

  • Johnson FB, Marciniak RA, McVey M, Stewart SA, Hahn WC, Guarente L (2001) The Saccharomyces cerevisiae WRN homolog Sgs1p participates in telomere maintenance in cells lacking telomerase. EMBO J 20:905–913

    CAS  PubMed Central  PubMed  Google Scholar 

  • Johnson RD, Jasin M (2001) Double-strand-break-induced homologous recombination in mammalian cells. Biochem Soc Trans 29:196–201

    CAS  PubMed  Google Scholar 

  • Kang LE, Symington LS (2000) Aberrant double-strand break repair in rad51 mutants of Saccharomyces cerevisiae. Mol Cell Biol 20:9162–9172

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kantake N, Sugiyama T, Kolodner RD, Kowalczykowski SC (2003) The recombination-deficient mutant RPA (rfa1-t11) is displaced slowly from single-stranded DNA by Rad51 protein. J Biol Chem 278:23410–23417

    CAS  PubMed  Google Scholar 

  • Kegel A, Sjostrand JO, Astrom SU (2001) Nej1p, a cell type-specific regulator of nonho-mologous end joining in yeast. Curr Biol 11:1611–1617

    CAS  PubMed  Google Scholar 

  • Keogh MC, Kim JA, Downey M, Fillingham J, Chowdhury D, Harrison JC, Onishi M, Datta N, Galicia S, Emili A, Lieberman J, Shen X, Buratowski S, Haber JE, Durocher D, Greenblatt JF, Krogan NJ (2005) A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery. Nature 439:497–501

    PubMed  Google Scholar 

  • Kramer KM, Brock JA, Bloom K, Moore JK, Haber JE (1994) Two different types of double-strand breaks in Saccharomyces cerevisiae are repaired by similar RAD52-independent, nonhomologous recombination events. Mol Cell Biol 14:1293–1301

    CAS  PubMed Central  PubMed  Google Scholar 

  • Krejci L, Van Komen S, Li Y, Villemain J, Reddy MS, Klein H, Ellenberger T, Sung P (2003) DNA helicase Srs2 disrupts the Rad51 presynaptic filament. Nature 423:305–309

    CAS  PubMed  Google Scholar 

  • Krogh BO, Symington LS (2004) Recombination proteins in yeast. Annu Rev Genet 38:233–71

    CAS  PubMed  Google Scholar 

  • Kupiec M, Petes TD (1988) Allelic and ectopic recombination between Ty elements in yeast. Genetics 119:549–559

    CAS  PubMed Central  PubMed  Google Scholar 

  • Labib K, Kearsey SE, Diffley JF (2001) MCM2-7 proteins are essential components of prereplicative complexes that accumulate cooperatively in the nucleus during G1-phase and are required to establish, but not maintain, the S-phase checkpoint. Mol Biol Cell 12:3658–3667

    CAS  PubMed Central  PubMed  Google Scholar 

  • Langston LD, Symington LS (2005) Opposing roles for DNA structure-specific proteins Rad1, Msh2, Msh3, and Sgs1 in yeast gene targeting. EMBO J 24:2214–2223

    CAS  PubMed Central  PubMed  Google Scholar 

  • Le S, Moore JK, Haber JE, Greider C (1999) RAD50 and RAD51 define two different pathways that collaborate to maintain telomeres in the absence of telomerase. Genetics 152:143–152

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lee SE, Bressan DA, Petrini JHJ, Haber JE (2002) Complementation between Nterminal Saccharomyces cerevisiae mre11 alleles in DNA repair and telomere length maintenance. DNA Repair 1:27–40

    CAS  PubMed  Google Scholar 

  • Lemoine FJ, Degtyareva NP, Lobachev K, Petes TD (2005) Chromosomal translocations in yeast induced by low levels of DNA polymerase a model for chromosome fragile sites. Cell 120:587–598

    CAS  PubMed  Google Scholar 

  • Lisby M, Mortensen UH, Rothstein R (2003) Colocalization of multiple DNA double-strand breaks at a single Rad52 repair centre. Nat Cell Biol 5:572–577

    CAS  PubMed  Google Scholar 

  • Lisby M, Rothstein R (2004) DNA damage checkpoint and repair centers. Curr Opin Cell Biol 16:328–334

    CAS  PubMed  Google Scholar 

  • Lundblad V, Blackburn EH (1993) An alternative pathway for yeast telomere maintenance rescues est1-senescence. Cell 73:347–360

    CAS  PubMed  Google Scholar 

  • Ma JL, Kim EM, Haber JE, Lee SE (2003) Yeast Mre11 and Rad1 proteins define a Kuindependent mechanism to repair double-strand breaks lacking overlapping end sequences. Mol Cell Biol 23:8820–8828

    CAS  PubMed Central  PubMed  Google Scholar 

  • Malkova A, Ivanov EL, Haber JE (1996) Double-strand break repair in the absence of RAD51 in yeast: a possible role for break-induced DNA replication. Proc Natl Acad Sci USA 93:7131–7136

    CAS  PubMed Central  PubMed  Google Scholar 

  • Malkova A, Ross L, Dawson D, Hoekstra MF, Haber JE (1996) Meiotic recombination initiated by a double-strand break in rad50 yeast cells otherwise unable to initiate meiotic recombination. Genetics 143:741–754

    CAS  PubMed Central  PubMed  Google Scholar 

  • Malkova A, Signon L, Schaefer CB, Naylor M, Theis JF, Newlon CS, Haber JE (2001) RAD51-independent break-induced replication to repair a broken chromosome depends on a distant enhancer site. Genes Dev 15:1055–1160

    CAS  PubMed Central  PubMed  Google Scholar 

  • Malkova A, Naylor M, Yamaguchi M, Ira G, Haber JE (2005) RAD51-dependent break-induced replication differs in kinetics and checkpoint responses from RAD51-mediated gene conversion. Mol Cell Biol 25:933–944

    CAS  PubMed Central  PubMed  Google Scholar 

  • Martin S, Laroche T, Suka N, Grunstein M, Gasser SM (1999) Relocalization of telomeric Ku and SIR proteins in response to DBA strand breaks in yeast. Cell 97:621–633

    CAS  PubMed  Google Scholar 

  • Mazina OM, Mazin AV, Nakagawa T, Kolodner RD, Kowalczykowski SC (2004) Saccharomyces cerevisiae Mer3 helicase stimulates 3’–5’ heteroduplex extension by Rad51; implications for crossover control in meiotic recombination. Cell 117:47–56

    CAS  PubMed  Google Scholar 

  • McDonald JP, Rothstein R (1994) Unrepaired heteroduplex DNA in Saccharomyces cere-visiae is decreased in RAD1 RAD52-independent recombination. Genetics 137:393–405

    CAS  PubMed Central  PubMed  Google Scholar 

  • McEachern MJ, Haber JE (2006) Break-Induced replication and recombinational telomere elongation in yeast. Annu Rev Biochem 75:111–135

    CAS  PubMed  Google Scholar 

  • McGill C, Shafer B, Strathern J (1989) Coconversion of flanking sequences with homothallic switching. Cell 57:459–467

    CAS  PubMed  Google Scholar 

  • Milne GT, Jin S, Shannon KB, Weaver DT (1996) Mutations in two Ku homologs define a DNA end-joining repair pathway in Saccharomyces cerevisiae. Mol Cell Biol 16:4189–4198

    CAS  PubMed Central  PubMed  Google Scholar 

  • Miyazaki T, Bressan DA, Shinohara M, Haber JE, Shinohara A (2004) In vivo assembly and disassembly of Rad51 and Rad52 complexes during double-strand break repair. EMBO J 23:939–949

    CAS  PubMed Central  PubMed  Google Scholar 

  • Moore JK, Haber JE (1996) Capture of retrotransposon DNA at the sites of chromosomal double-strand breaks. Nature 383:644–646

    PubMed  Google Scholar 

  • Moore JK, Haber JE (1996) Cell cycle and genetic requirements of two pathways of non-homologous end-joining repair of double-strand breaks in Saccharomyces cerevisiae. Mol Cell Biol 16:2164–2173

    CAS  PubMed Central  PubMed  Google Scholar 

  • Moreau S, Ferguson JR, Symington LS (1999) The nuclease activity of Mre11 is required for meiosis but not for mating type switching, end joining or telomere maintenance. Mol Cell Biol 19:556–566

    CAS  PubMed Central  PubMed  Google Scholar 

  • Morrow DM, Connelly C, Hieter P (1997) “Break copy” duplication: a model for chromo-some fragment formation in Saccharomyces cerevisiae. Genetics 147:371–382

    CAS  PubMed Central  PubMed  Google Scholar 

  • Natarajan S, McEachern MJ (2002) Recombinational telomere elongation promoted by DNA circles. Mol Cell Biol 22:4512–4521

    CAS  PubMed  Google Scholar 

  • Nickoloff JA, Sweetser DB, Khalsa GJ, Wheeler SL (1999) Multiple heterologies increase the length of double-strand break-induced allelic gene conversion tracts. Genetics 153:665–679

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nickoloff JA, Brenneman MA (2004) Analysis of recombinational repair of DNA double-strand breaks in mammalian cells with I-SceI nuclease. Methods Mol Biol 262:35–52

    CAS  PubMed  Google Scholar 

  • Ooi SL, Boeke JD (2001) A DNA microarray-based genetic screen for nonhomologous end-joining mutants in Saccharomyces cerevisiae. Science 294:2552–2556

    CAS  PubMed  Google Scholar 

  • Osman F, Dixon J, Doe CL, Whitby MC (2003) Generating crossovers by resolution of nicked Holliday junctions: a role for Mus81-Eme1 in meiosis. Mol Cell 12:761–774

    CAS  PubMed  Google Scholar 

  • Ozenberger BA, Roeder GS (1991) A unique pathway of double-strand break repair operates in tandemly repeated genes. Mol Cell Biol 11:1222–1231

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pâques F, Leung WY, Haber JE (1998) Expansions and contractions in a tandem repeat induced by double-strand break repair. Mol Cell Biol 18:2045–2054

    PubMed Central  PubMed  Google Scholar 

  • Pâques F, Haber JE (1999) Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 63:349–404

    PubMed Central  PubMed  Google Scholar 

  • Pâques F, Richard G-F, Haber JE (2001) Expansions and contractions in 36-bp minisatellite by gene conversion in yeast. Genetics 158:155–166

    PubMed Central  PubMed  Google Scholar 

  • Plessis A, Perrin A, Haber JE, Dujon B (1992) Site-specific recombination determined by I-SceI, a mitochondrial group I intron-encoded endonuclease expressed in the yeast nucleus. Genetics 130:451–460

    CAS  PubMed Central  PubMed  Google Scholar 

  • Porteus MH (2006) Mammalian gene targeting with designed zinc finger nucleases. Mol Ther 13:438–446

    CAS  PubMed  Google Scholar 

  • Prado F, Aguilera A (2003) Control of cross-over by single-strand DNA resection. Trends Genet 19:428–431

    CAS  PubMed  Google Scholar 

  • Prakash R, Krejci L, Van Komen S, Anke Schurer K, Kramer W, Sung P (2005) Saccharomyces cerevisiae MPH1 gene, required for homologous recombination-mediated mutation avoidance, encodes a 3’ to 5’ DNA helicase. J Biol Chem 280:7854–7860

    CAS  PubMed  Google Scholar 

  • Prudden J, Evans JS, Hussey SP, Deans B, O’Neill P, Thacker J, Humphrey T (2003) Path-way utilization in response to a site-specific DNA double-strand break in fission yeast. EMBO J 22:1419–1430

    CAS  PubMed Central  PubMed  Google Scholar 

  • Putnam CD, Pennaneach V, Kolodner RD (2004) Chromosome healing through terminal deletions generated by de novo telomere additions in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 101:13262–13267

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ray BL, White CI, Haber JE (1991) Heteroduplex formation and mismatch repair of the “stuck” mutation during mating-type switching in Saccharomyces cerevisiae. Mol Cell Biol 11:5372–5380

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ricchetti M, Fairhead C, Dujon B (1999) Mitochondrial DNA repairs double-strand breaks in yeast chromosomes. Nature 402:96–100

    CAS  PubMed  Google Scholar 

  • Richard GF, Dujon B, Haber JE (1999) Double-strand break repair can lead to high frequencies of deletions within short CAG/CTG trinucleotide repeats. Mol Gen Genet 261:871–882

    CAS  PubMed  Google Scholar 

  • Rodrigue A, Lafrance M, Gauthier MC, McDonald D, Hendzel M, West SC, Jasin M, Masson JY (2006) Interplay between human DNA repair proteins at a unique double-strand break in vivo. EMBO J 25:222–231

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rong YS, Titen SW, Xie HB, Golic MM, Bastiani M, Bandyopadhyay P, Olivera BM, Brodsky M, Rubin GM, Golic KG (2002) Targeted mutagenesis by homologous recombination in D. melanogaster. Genes Dev 16:1568–1581

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schär P, Herrmann G, Daly G, Lindahl T (1997) A newly identified DNA ligase of Saccharomyces cerevisiae involved in RAD52-independent repair of DNA double-strand breaks. Genes Dev 11:1912–1924

    PubMed Central  PubMed  Google Scholar 

  • Scheller J, Schurer A, Rudolph C, Hettwer S, Kramer W (2000) MPH1:a yeast gene encoding a DEAH protein, plays a role in protection of the genome from spontaneous and chemically induced damage. Genetics 155:1069–1081

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schurer KA, Rudolph C, Ulrich HD, Kramer W (2004) Yeast MPH1 gene functions in an error-free DNA damage bypass pathway that requires genes from homologous recombination, but not from postreplicative repair. Genetics 166:1673–1686

    PubMed Central  PubMed  Google Scholar 

  • Schwacha A, Kleckner N (1995) Identification of double Holliday junctions as intermediates in meiotic recombination. Cell 83:783–791

    CAS  PubMed  Google Scholar 

  • Shim EY, Ma JL, Oum JH, Yanez Y, Lee SE (2005) The yeast chromatin remodeler RSC complex facilitates end joining repair of DNA double-strand breaks. Mol Cell Biol 25:3934–3944

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shroff R, Arbel-Eden A, Pilch D, Ira G, Bonner WM, Petrini JH, Haber JE, Lichten M (2004) Distribution and dynamics of chromatin modification induced by a defined DNA double-strand break. Curr Biol 14:1703–1711

    CAS  PubMed  Google Scholar 

  • Signon L, Malkova A, Naylor M, Haber JE (2001) Genetic requirements for RAD51-and RAD54-independent break-induced replication repair of a chromosomal double-strand break. Mol Cell Biol 21:2048–2056

    CAS  PubMed Central  PubMed  Google Scholar 

  • Smith GR, Boddy MN, Shanahan P, Russell P (2003) Fission yeast Mus81. Eme1 Holliday junction resolvase is required for meiotic crossing over but not for gene conversion. Genetics 165:2289–2293

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sonoda E, Sasaki MS, Buerstedde JM, Bezzubova O, Shinohara A, Ogawa H, Takata M, Yamaguchi-Iwai Y, Takeda S (1998) Rad51-deficient vertebrate cells accumulate chromosomal breaks prior to cell death. EMBO J 17:598–608

    CAS  PubMed Central  PubMed  Google Scholar 

  • Studamire B, Price G, Sugawara N, Haber JE, Alani E (1999) Separation-of-function mutations in Saccharomyces cerevisiae MSH2 that confer mismatch repair defects but do not affect nonhomologous-tail removal during recombination. Mol Cell Biol 19:7558–7567

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sugawara N, Haber JE, unpublished results

    Google Scholar 

  • Sugawara N, Paques F, Colaiacovo M, Haber JE (1997) Role of Saccharomyces cerevisiae Msh2 and Msh3 repair proteins in double-strand break-induced recombination. Proc Natl Acad Sci USA 94:9214–9219

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sugawara N, Ira G, Haber JE (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

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sugawara N, Wang X, Haber JE (2003) In vivo roles of Rad52, Rad54, and Rad55 proteins in Rad51-mediated recombination. Mol Cell 12:209–219

    CAS  PubMed  Google Scholar 

  • Sugawara N, Goldfarb T, Studamire B, Alani E, Haber JE (2004) Heteroduplex rejection during single-strand annealing requires Sgs1 helicase and mismatch repair proteins Msh2 and Msh6 but not Pms1. Proc Natl Acad Sci USA 101:9315–9320

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sugiyama T, Kowalczykowski SC (2002) Rad52 protein associates with RPA-ssDNA to accelerate Rad51-mediated displacement of RPA and presynaptic complex formation. J Biol Chem 277:31663–31672

    CAS  PubMed  Google Scholar 

  • Sung P (1997a) Function of yeast Rad52 protein as a mediator between replication protein A and the Rad51 recombinase. J Biol Chem 272:28194–28197

    CAS  PubMed  Google Scholar 

  • Sung P (1997b) Yeast Rad55 and Rad57 proteins form a heterodimer that functions with replication protein A to promote DNA strand exchange by Rad51 recombinase. Genes Dev 11:1111–1121

    CAS  PubMed  Google Scholar 

  • Szostak JW, Orr WT, Rothstein RJ, Stahl FW (1983) The double-strand-break repair model for recombination. Cell 33:25–35

    CAS  PubMed  Google Scholar 

  • Teng S, Chang J, McCowan B, Zakian VA (2000) Telomerase-independent lengthening of yeast telomeres occurs by an abrupt Rad50p-dependent, Rif-inhibited recombinational process. Mol Cell 6:947–952

    CAS  PubMed  Google Scholar 

  • Teng SC, Kim B, Gabriel A (1996) Retrotransposon reverse-transcriptase-mediated repair of chromosomal breaks. Nature 383:641–644

    PubMed  Google Scholar 

  • Teng SC, Zakian VA (1999) Telomere-telomere recombination is an efficient bypass path-way for telomere maintenance in Saccharomyces cerevisiae. Mol Cell Biol 19:8083–8093

    CAS  PubMed Central  PubMed  Google Scholar 

  • Teo SH, Jackson SP (2000) Lif1p targets the DNA ligase Lig4p to sites of DNA double-strand breaks. Curr Biol 10:165–168

    CAS  PubMed  Google Scholar 

  • Tsubouchi H, Ogawa H (1998) A novel mre11 mutation impairs processing of double-strand breaks of DNA during both mitosis and meiosis. Mol Cell Biol 18:260–268

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tsukamoto Y, Kato J, Ikeda H (1996) Effects of mutations of RAD50, RAD51, RAD52, and related genes on illegitimate recombination in Saccharomyces cerevisiae. Genetics 142:383–391

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tsukamoto Y, Taggart AK, Zakian VA (2001) The role of the Mre11-Rad50-Xrs2 complex in telomerase-mediated lengthening of Saccharomyces cerevisiae telomeres. Curr Biol 11:1328–1335

    CAS  PubMed  Google Scholar 

  • Ubersax JA, Woodbury EL, Quang PN, Paraz M, Blethrow JD, Shah K, Shokat KM, Morgan DO (2003) Targets of the cyclin-dependent kinase Cdk1. Nature 425:859–964

    CAS  PubMed  Google Scholar 

  • Umezu K, Sugawara N, Chen C, Haber JE, Kolodner RD (1998) Genetic analysis of yeast RPA1 reveals its multiple functions in DNA metabolism. Genetics 148:989–1005

    CAS  PubMed Central  PubMed  Google Scholar 

  • Valencia M, Bentele M, Vaze MB, Herrmann G, Kraus E, Lee SE, Schar P, Haber JE (2001) NEJ1 controls non-homologous end joining in Saccharomyces cerevisiae. Nature 414:666–669

    CAS  PubMed  Google Scholar 

  • van Attikum H, Fritsch O, Hohn B, Gasser SM (2004) Recruitment of the INO80 complex by H2A phosphorylation links ATP-dependent chromatin remodeling with DNA double-strand break repair. Cell 119:777–788

    PubMed  Google Scholar 

  • Vaze M, Pellicioli A, Lee S, Ira G, Liberi G, Arbel-Eden A, Foiani M, Haber JE (2002) Recovery from checkpoint-mediated arrest after repair of a double-strand break requires srs2 helicase. Mol Cell 10:373–385

    CAS  PubMed  Google Scholar 

  • Veaute X, Jeusset J, Soustelle C, Kowalczykowski SC, Le Cam E, Fabre F (2003) The Srs2 helicase prevents recombination by disrupting Rad51 nucleoprotein filaments. Nature 423:309–312

    CAS  PubMed  Google Scholar 

  • Voelkel-Meiman K, Roeder GS (1990) Gene conversion tracts stimulated by HOT1-promoted transcription are long and continuous. Genetics 126:851–867

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang X, Haber JE (2004) Role of Saccharomyces single-stranded DNA-binding protein RPA in the strand invasion step of double-strand break repair. PLoS Biol 2:104–111

    CAS  Google Scholar 

  • Wang X, Ira G, Tercero JA, Holmes AM, Diffley JF, Haber JE (2004) Role of DNA replication proteins in double-strand break-induced recombination in Saccharomyces cerevisiae. Mol Cell Biol 24:6891–6899

    CAS  PubMed Central  PubMed  Google Scholar 

  • Watt PM, Hickson ID, Borts RH, Louis EJ (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

    CAS  PubMed Central  PubMed  Google Scholar 

  • Weiss K, Simpson RT (1998) High-resolution structural analysis of chromatin at specific loci: Saccharomyces cerevisiae silent mating type locus HMLα. Mol Cell Biol 18:5392–5403

    CAS  PubMed Central  PubMed  Google Scholar 

  • White CI, Haber JE (1990) Intermediates of recombination during mating type switching in Saccharomyces cerevisiae. EMBO J 9:663–673

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wilson S, Warr N, Taylor DL, Watts FZ (1999) The role of Schizosaccharomyces pombe Rad32, the Mre11 homologue, and other DNA damage response proteins in non-homologous end joining and telomere length maintenance. Nucleic Acids Res 27:2655–2661

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wilson TE, Grawunder U, Lieber MR (1997) Yeast DNA ligase IV mediates non-homologous DNA end joining. Nature 388:495–498

    CAS  PubMed  Google Scholar 

  • Wilson TE, Lieber MR (1999) Efficient processing of DNA ends during yeast nonhomolo-gous end joining. Evidence for a DNA polymerase beta (Pol4)-dependent pathway. J Biol Chem 274:23599–23609

    CAS  PubMed  Google Scholar 

  • Wilson TE (2002) A genomics-based screen for yeast mutants with an altered recombination/end-joining repair ratio. Genetics 162:677–688

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wolner B, van Komen S, Sung P, Peterson CL (2003) Recruitment of the recombinational repair machinery to a DNA double-strand break in yeast. Mol Cell 12:221–232

    CAS  PubMed  Google Scholar 

  • Wright DA, Townsend JA, Winfrey RJ Jr, Irwin PA, Rajagopal J, Lonosky PM, Hall BD, Jondle MD, Voytas DF (2005) High-frequency homologous recombination in plants mediated by zinc-finger nucleases. Plant J 44:693–705

    CAS  PubMed  Google Scholar 

  • Wu L, Hickson ID (2003) The Bloom’s syndrome helicase suppresses crossing over during homologous recombination. Nature 426:870–874

    CAS  PubMed  Google Scholar 

  • Wu X, Haber JE (1996) A 700 bp cisacting region controls mating-type dependent recombination along the entire left arm of yeast chromosome III. Cell 87:277–285

    CAS  PubMed  Google Scholar 

  • Wu X, Wu C, Haber JE (1997) Rules of donor preference in Saccharomyces mating-type gene switching revealed by a competition assay involving two types of recombination. Genetics 147:399–407

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yamaguchi-Iwai Y, Sonoda E, Sasaki MS, Morrison C, Haraguchi T, Hiraoka Y, Yamashita YM, Yagi T, Takata M, Price C, Kakazu N, Takeda S (1999) Mre11 is essential for the maintenance of chromosomal DNA in vertebrate cells. EMBO J 18:6619–6629

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yu X, Gabriel A (2004) Reciprocal translocations in Saccharomyces cerevisiae formed by nonhomologous end joining. Genetics 166:741–751

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zubko MK, Guillard S, Lydall D (2004) Exo1 and Rad24 differentially regulate generation of ssDNA at telomeres of Saccharomyces cerevisiae cdc13-1 mutants. Genetics 168:103–115

    CAS  PubMed Central  PubMed  Google Scholar 

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  1. Rosenstiel Center and Department of Biology, Brandeis University, Waltham, MA, 02454-9110, USA

    James E. Haber

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  1. James E. Haber
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  1. Centro Andaluz de Biologia Molecular y Medicina Regenerativa CABIMER, CSIC-Universidad de Sevilla, Av. Américo Vespucio s/n, 41092, Sevilla, Spain

    Andrés Aguilera

  2. Department of Genetics & Development, Columbia University Medical Center, 701 West 168th Street, HHSC 1608, New York, NY, 10032-2704, USA

    Rodney Rothstein

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Haber, J.E. (2007). Multiple mechanisms of repairing meganuclease-induced double-strand DNA breaks in budding yeast. In: Aguilera, A., Rothstein, R. (eds) Molecular Genetics of Recombination. Topics in Current Genetics, vol 17. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-71021-9_10

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