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Biochemistry of eukaryotic homologous recombination

  • Chapter
Molecular Genetics of Recombination

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

Abstract

The biochemistry of eukaryotic homologous recombination caught fire with the discovery that Rad51 is the eukaryotic homolog of the bacterial RecA and T4 UvsX proteins; and this field is still hot. The core reaction of homologous recombination, homology search and DNA strand invasion, along with the proteins catalyzing it, are conserved throughout evolution in principle. However, the increased complexity of eukaryotic genomes and the diversity of eukaryotic cell biology pose additional challenges to the recombination machinery. It is not surprising that this increase in complexity coincided with the evolution of new recombination proteins and novel support pathways, as well as changes in the properties of those eukaryotic recombination proteins that are evidently conserved in evolution. In humans, defects in homologous recombination lead to increased cancer predisposition, underlining the importance of this pathway for genomic stability and tumor suppression. This review will focus on the mechanisms of homologous recombination in eukaryotes as elucidated by the biochemical analysis of yeast and human proteins.

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References

  • Aboussekhra A, Chanet R, Adjiri A, Fabre F (1992) Semidominant suppressors of Srs2 helicase mutations of Saccharomyces cerevisiae map in the RAD51 gene, whose sequence predicts a protein with similarities to procaryotic RecA protein. Mol Cell Biol 12:3224–3234

    CAS  PubMed Central  PubMed  Google Scholar 

  • Aboussekhra A, Chanet R, Zgaga Z, Cassier Chauvat C, Heude M, Fabre F (1989) RADH, a gene of Saccharomyces cerevisiae encoding a putative DNA helicase involved in DNA repair. Characteristics of radH mutants and sequence of the gene. Nucl Acids Res 17:7211–7219

    CAS  PubMed Central  PubMed  Google Scholar 

  • Aguilera A, Klein HL (1988) Genetic control of intrachromosomal recombination in Saccharomyces cerevisiae. I. Isolation and genetic characterization of hyper-recombination mutations. Genetics 119:779–790

    CAS  PubMed Central  PubMed  Google Scholar 

  • Aihara H, Ito Y, Kurumizaka H, Yokoyama S, Shibata T (1999) The Nterminal domain of the human Rad51 protein binds DNA: Structure and a DNA binding surface as revealed by NMR. J Mol Biol 290:495–504

    CAS  PubMed  Google Scholar 

  • Alexeev A, Mazin A, Kowalczykowski SC (2003) Rad54 protein possesses chromatin-remodeling activity stimulated by a Rad51-ssDNA nucleoprotein filament. Nature Struct Biol 10:182–186

    CAS  PubMed  Google Scholar 

  • Alexiadis V, Kadonaga JT (2003) Strand pairing by Rad54 and Rad51 is enhanced by chromatin. Genes Dev 16:2767–2771

    Google Scholar 

  • Amitani I, Baskin RJ, Kowalczykowski S (2006) Direct visualization of a chromatin-remodeling protein, Rad54, translocating along single-molecules of double-stranded DNA. Mol Cell 23:143–148

    CAS  PubMed  Google Scholar 

  • Aylon Y, Liefshitz B, Bitan-Banin G, Kupiec M (2003) Molecular dissection of mitotic re-combination in the yeast Saccharomyces cerevisiae. Mol Cell Biol 23:1403–1417

    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 

  • Bashkirov VI, Herzberg K, Rolfsmeier M, Heyer W-D (2006) Rad55 phopshorylation on serines 2,8,14 is required for efficient recombinational DNA repair and recovery of stalled replication forks. Mol Cell Biol, in press

    Google Scholar 

  • Bashkirov VI, King JS, Bashkirova EV, Schmuckli-Maurer J, Heyer WD (2000) DNA re-pair protein Rad55 is a terminal substrate of the DNA damage checkpoints. Mol Cell Biol 20:4393–4404

    CAS  PubMed Central  PubMed  Google Scholar 

  • Baumann P, Benson FE, West SC (1996) Human Rad51 protein promotes ATP-dependent homologous pairing and strand transfer reactions in vitro. Cell 87:757–766

    CAS  PubMed  Google Scholar 

  • Baumann P, West SC (1997) The human Rad51 protein: polarity of strand transfer and stimulation by hRP-A. EMBO J 16:5198–5206

    CAS  PubMed Central  PubMed  Google Scholar 

  • Beernink HTH, Morrical SW (1999) RMPs: Recombination/replication mediator proteins. Trends Biochem Sci 24:385–389

    CAS  PubMed  Google Scholar 

  • Benson FE, Baumann P, West SC (1998) Synergistic actions of Rad51 and Rad52 in re-combination and DNA repair. Nature 391:401–404

    CAS  PubMed  Google Scholar 

  • Bianco PR, Tracy RB, Kowalczykowski SC (1998) DNA strand exchange proteins: a bio-chemical and physical comparison. Front Biosci 3:570–603

    Google Scholar 

  • Bochkarev A, Bochkareva E (2004) From RPA to BRCA2: lessons from single-stranded DNA binding by the OB-fold. Curr Opin Struct Biol 14:36–42

    CAS  PubMed  Google Scholar 

  • Boddy MN, Lopez-Girona A, Shanahan P, Interthal H, Heyer WD, Russell P (2000) Damage tolerance protein Mus81 associates with the FHA1 domain of checkpoint kinase Cds1. Mol Cell Biol 20:8758–8766

    CAS  PubMed Central  PubMed  Google Scholar 

  • Braybrooke JP, Li JL, Wu L, Caple F, Benson FE, Hickson ID (2003) Functional interac-tion between the Bloom’s syndrome helicase and the RAD51 paralog, RAD51L3 (RAD51D). J Biol Chem 278:48357–48366

    CAS  PubMed  Google Scholar 

  • Bugreev DV, Mazin AV (2004) Ca2+ activates human homologous recombination protein Rad51 by modulating its ATPase activity. Proc Natl Acad Sci USA 101:9988–9993

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bugreev DV, Mazina OM, Mazin A (2006) Rad54 protein promotes branch migration of Holliday junctions. Nature 442:590–593

    CAS  PubMed  Google Scholar 

  • Chen G, Yuan SSF, Liu W, Xu Y, Trujillo K, Song BW, Cong F, Goff SP, Wu Y, Arlinghaus R, Baltimore D, Gasser PJ, Park MS, Sung P, Lee E (1999) Radiation-induced assembly of Rad51 and Rad52 recombination complex requires ATM and c-Abl. J Biol Chem 274:12748–12752

    CAS  PubMed  Google Scholar 

  • Chi P, Van Komen S, Sehorn MG, Sigurdsson S, Sung P (2006) Roles of ATP binding and ATP hydrolysis in human Rad51 recombinase function. DNA Repair (Amst) 5:381–391

    CAS  Google Scholar 

  • Clever B, Interthal H, Schmuckli-Maurer J, King J, Sigrist M, Heyer WD (1997) Recombi-national repair in yeast: Functional interactions between Rad51 and Rad54 proteins. EMBO J 16:2535–2544

    CAS  PubMed Central  PubMed  Google Scholar 

  • Clever B, Schmuckli-Maurer J, Sigrist M, Glassner B, Heyer W-D (1999) Specific negative effects resulting from elevated levels of the recombinational repair protein Rad54p in Saccharomyces cerevisiae. Yeast 15:721–740

    CAS  PubMed  Google Scholar 

  • Constantinou A, Chen XB, McGowan CH, West SC (2002) Holliday junction resolution in human cells: two junction endonucleases with distinct substrate specificities. EMBO J 21:5577–5585

    CAS  PubMed Central  PubMed  Google Scholar 

  • Conway AB, Lynch TW, Zhang Y, Fortin GS, Fung CW, Symington LS, Rice PA (2004) Crystal structure of a Rad51 filament. Nat Rev Struc Mol Biol 11:791–796

    CAS  Google Scholar 

  • Davis AP, Symington LS (2001) The yeast recombinational repair protein Rad59 interacts with Rad52 and stimulates single-strand annealing. Genetics 159:515–525

    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 

  • Donovan JW, Milne GT, Weaver DT (1994) Homotypic and heterotypic protein associations control Rad51 function in double-strand break repair. Genes Dev 8:2552–2562

    CAS  PubMed  Google Scholar 

  • Egelman EH (2003) A tale of two polymers: New insights into helical filaments. Nat Rev Mol Cell Biol 4:621–630

    CAS  PubMed  Google Scholar 

  • Esashi F, Christ N, Gannon J, Liu YL, Hunt T, Jasin M, West SC (2005) CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for recombinational repair. Nature 434:598–604

    CAS  PubMed  Google Scholar 

  • Fortin GS, Symington LS (2002) Mutations in yeast Rad51 that partially bypass the requirement for Rad55 and Rad57 in DNA repair by increasing the stability of Rad51-DNA complexes. EMBO J 21:3160–3170

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fricke WM, Bastin-Shanower SA, Brill SJ (2005) Substrate specificity of the Saccharomyces cerevisiae Mus81-Mms4 endonuclease. DNA Repair 4:243–251

    CAS  PubMed  Google Scholar 

  • Fujimori A, Tachiiri S, Sonoda E, Thompson LH, Dhar PK, Hiraoka M, Takeda S, Zhang Y, Reth M, Takata M (2001) Rad52 partially substitutes for the Rad51 paralog XRCC3 in maintaining chromosomal integrity in vertebrate cells. EMBO J 20:5513–5520

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gaillard P-H, Noguchi E, Shanahan P, Russell P (2003) The endogenous Mus81-Eme1 complex resolves Holliday junctions by a nick and counternick mechanism. Mol Cell 12:747–759

    CAS  PubMed  Google Scholar 

  • Galkin VE, Wu Y, Zhang X-P, Qian X, He Y, Yu X, Heyer W-D, Luo Y, Egelman EH (2006) The RAD51/RadA Nterminal domain activates nucleoprotein filaments. Structure 14:983–992

    CAS  PubMed  Google Scholar 

  • Gasior SL, Olivares H, Ear U, Hari DM, Weichselbaum R, Bishop DK (2001) Assembly of RecA-like recombinases: Distinct roles for mediator proteins in mitosis and meiosis. Proc Natl Acad Sci USA 98:8411–8418

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gasior SL, Wong AK, Kora Y, Shinohara A, Bishop DK (1998) Rad52 associates with RPA and functions with Rad55 and Rad57 to assemble meiotic recombination complexes. Genes Dev 12:2208–2221

    CAS  PubMed Central  PubMed  Google Scholar 

  • Golub EI, Kovalenko OV, Gupta RC, Ward DC, Radding CM (1997) Interaction of human recombination proteins Rad51 and Rad54. Nucleic Acids Res 25:4106–4110

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gupta RC, Folta-Stogniew E, O’Malley S, Takahashi M, Radding CM (1999) Rapid exchange of A: T base pairs is essential for recognition of DNA homology by human Rad51 recombination protein. Mol Cell 4:705–714

    CAS  PubMed  Google Scholar 

  • Haber JE, Heyer WD (2001) The fuss about Mus81. Cell 107:551–554

    CAS  PubMed  Google Scholar 

  • Hays SL, Firmenich AA, Berg P (1995) Complex formation in yeast double-strand break repair: Participation of Rad51, Rad52, Rad55, and Rad57 proteins. Proc Natl Acad Sci USA 92:6925–6929

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hays SL, Firmenich AA, Massey P, Banerjee R, Berg P (1998) Studies of the interaction between Rad52 protein and the yeast single-stranded DNA binding protein RPA. Mol Cell Biol 18:4400–4406

    CAS  PubMed Central  PubMed  Google Scholar 

  • Heyer WD, Ehmsen KT, Solinger JA (2003) Holliday junctions in the eukaryotic nucleus: Resolution in sight? Trends Biochem Sci 10:548–557

    Google Scholar 

  • Heyer WD, Li XR, Rolfsmeier M, Zhang X-P (2006) Rad54: the Swiss Army knife of homologous recombination? Nucleic Acids Res: in press

    Google Scholar 

  • Holbeck SL, Strathern JN (1997) A role for REV3 in mutagenesis during double-strand break repair in Saccharomyces cerevisiae. Genetics 147:1017–1024

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hollingsworth NM, Brill SJ (2004) The Mus81 solution to resolution: generating meiotic crossovers without Holliday junctions. Genes Dev 18:117–125

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hunter N, Chambers SR, Louis EJ, Borts RH (1996) The mismatch repair system contributes to meiotic sterility in an interspecific yeast hybrid. EMBO J 15:1726–1733

    CAS  PubMed Central  PubMed  Google Scholar 

  • Interthal H, Heyer WD (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

    CAS  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 

  • 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 

  • Jaskelioff M, Van Komen S, Krebs JE, Sung P, Peterson CL (2003) Rad54p is a chromatin remodeling enzyme required for heteroduplex joint formation with chromatin. J Biol Chem 278:9212–9218

    CAS  PubMed  Google Scholar 

  • Jiang H, Xie YQ, Houston P, Stemke-Hale K, Mortensen UH, Rothstein R, Kodadek T (1996) Direct association between the yeast Rad51 and Rad54 recombination proteins. J Biol Chem 271:33181–33186

    CAS  PubMed  Google Scholar 

  • Johnson RD, Symington LS (1995) Functional differences and interactions among the putative RecA homologs RAD51, RAD55, and RAD57. Mol Cell Biol 15:4843–4850

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kagawa W, Kurumizaka H, Ishitani R, Fukai S, Nureki O, Shibata T, Yokoyama S (2002) Crystal structure of the homologouspairing domain from the human Rad52 recombinase in the undecameric form. Mol Cell 10:359–371

    CAS  PubMed  Google Scholar 

  • Kantake N, Madiraju M, Sugiyama T, Kowalczykowski C (2002) Escherichia coli RecO protein anneals ssDNA complexed with its cognate ssDNA-binding protein: A common step in genetic recombination. Proc Natl Acad Sci USA 99:15327–15332

    CAS  PubMed Central  PubMed  Google Scholar 

  • Karow JK, Constantinou A, Li JL, West SC, Hickson ID (2000) The Bloom’s syndrome gene product promotes branch migration of Holliday junctions. Proc Natl Acad Sci USA 97:6504–6508

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kawamoto T, Araki K, Sonoda E, Yamashita YM, Harada K, Kikuchi K, Masutani C, Hanaoka F, Nozaki K, Hashimoto N, Takeda S (2005) Dual roles for DNA polymerase eta in homologous DNA recombination and translesion DNA synthesis. Mol Cell 20:793–799

    CAS  PubMed  Google Scholar 

  • Kiianitsa K, Solinger JA, Heyer WD (2002) Rad54 protein exerts diverse modes of ATPase activity on duplex DNA partially and fully covered with Rad51 protein. J Biol Chem 277:46205–46215

    CAS  PubMed  Google Scholar 

  • Kiianitsa K, Solinger JA, Heyer WD (2006) Terminal association of the Rad54 protein with the Rad51-dsDNA filament. Proc Natl Acad Sci USA 103:9767–9772

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kim PM, Paffett KS, Solinger JA, Heyer WD, Nickoloff JA (2002) Spontaneous and double-strand break-induced recombination, and gene conversion tract lengths, are differentially affected by overexpression of wild-type or ATPase-defective yeast Rad54. Nucleic Acids Res 30:2727–2735

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kleff S, Kemper B, Sternglanz R (1992) Identification and characterization of yeast mutants and the gene for a cruciform cutting endonuclease. EMBO J 11:699–704

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kowalczykowski SC, Dixon DA, Eggleston AK, Lauder SD, Rehrauer WM (1994) Bio-chemistry of homologous recombination in Escherichia coli. Microbiol Rev 58:401–465

    CAS  PubMed Central  PubMed  Google Scholar 

  • Krejci L, Song BW, Bussen W, Rothstein R, Mortensen UH, Sung P (2002) Interaction with Rad51 is indispensable for recombination mediator function of Rad52. J Biol Chem 277:40132–40141

    CAS  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 38:233–271

    CAS  PubMed  Google Scholar 

  • Kurumizaka H, Ikawa S, Nakada M, Eda K, Kagawa W, Takata M, Takeda S, Yokoyama S, Shibata T (2001) Homologous-pairing activity of the human DNA-repair proteins Xrcc3. Rad51C. Proc Natl Acad Sci USA 98:5538–5543

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kurumizaka H, Ikawa S, Nakada M, Enomoto R, Kagawa W, Kinebuchi T, Yamazoe M, Yokoyama S, Shibata T (2002) Homologous pairing and ring and filament structure formation activities of the human Xrcc2*Rad51D complex. J Biol Chem 277:14315–14320

    CAS  PubMed  Google Scholar 

  • Liberi G, Chiolo I, Pellicioli A, Lopes M, Plevani P, Muzi-Falconi M, Foiani M (2000) Srs2 DNA helicase is involved in checkpoint response and its regulation requires a functional Mec1-dependent pathway and Cdk1 activity. EMBO J 19:5027–5038

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lio YC, Mazin AV, Kowalczykowski SC, Chen DJ (2003) Complex formation by the human Rad51B and Rad51C DNA repair proteins and their activities in vitro. J Biol Chem 278:2469–2478

    CAS  PubMed  Google Scholar 

  • Lisby M, Barlow JH, Burgess RC, Rothstein R (2004) Choreography of the DNA damage response: Spatiotemporal relationships among checkpoint and repair proteins. Cell 118:699–713

    CAS  PubMed  Google Scholar 

  • Liu J, Bond JP, Morrical SW (2006) Mechanism of presynaptic filament stabilization by the bacteriophage T4 UvsY recombination mediator protein. Biochemistry 45:5493–5502

    CAS  PubMed  Google Scholar 

  • Liu YL, Masson JY, Shah R, O’Regan P, West SC (2004) RAD51C is required for Holliday junction processing in mammalian cells. Science 303:243–246

    CAS  PubMed  Google Scholar 

  • Mankouri HW, Craig TJ, Morgan A (2002) SGS1 is a multicopy suppressor of srs2: functional overlap between DNA helicases. Nucleic Acids Res 30:1103–1113

    CAS  PubMed Central  PubMed  Google Scholar 

  • Martin V, Chahwan C, Gao H, Blais V, Wohlschlegel J, Yates JR 3rd, McGowan CH, Russell P (2006) Sws1 is a conserved regulator of homologous recombination in eukaryotic cells. EMBO J 25:2564–2574

    CAS  PubMed Central  PubMed  Google Scholar 

  • Masson JY, Stasiak AZ, Stasiak A, Benson FE, West SC (2001a) Complex formation by the human RAD51C and XRCC3 recombination repair proteins. Proc Natl Acad Sci USA 98:8440–8446

    CAS  PubMed Central  PubMed  Google Scholar 

  • Masson JY, Tarsounas MC, Stasiak AZ, Stasiak A, Shah R, McIlwraith MJ, Benson FE, West SC (2001b) Identification and purification of two distinct complexes containing the five RAD51 paralogs. Genes Dev 15:3296–3307

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mazin AV, Alexeev AA, Kowalczykowski SC (2003) A novel function of Rad54 protein — Stabilization of the Rad51 nucleoprotein filament. J Biol Chem 278:14029–14036

    CAS  PubMed  Google Scholar 

  • Mazin AV, Bornarth CJ, Solinger JA, Heyer W-D, Kowalczykowski SC (2000a) Rad54 protein is targeted to pairing loci by the Rad51 nucleoprotein filament. Mol Cell 6:583–592

    CAS  PubMed  Google Scholar 

  • Mazin AV, Zaitseva E, Sung P, Kowalczykowski SC (2000b) Tailed duplex DNA is the preferred substrate for Rad51 protein-mediated homologous pairing. EMBO J 19:1148–1156

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mazin OM, Mazin AW (2004) Human Rad54 protein stimulates DNA strand exchange activity of hRad51 protein in the presence of Ca2+. J Biol Chem 279:52041–52051

    Google Scholar 

  • McIlwraith MJ, Vaisman A, Liu YL, Fanning E, Woodgate R, West SC (2005) Human DNA polymerase eta promotes DNA synthesis from strand invasion intermediates of homologous recombination. Mol Cell 20:783–792

    CAS  PubMed  Google Scholar 

  • Morimatsu K, Kowalczykowski SC (2003) RecFOR proteins load RecA protein onto gapped DNA to accelerate DNA strand exchange: A universal step of recombinational repair. Mol Cell 11:1337–1347

    CAS  PubMed  Google Scholar 

  • Morishita T, Furukawa F, Sakaguchi C, Toda T, Carr AM, Iwasaki H, Shinagawa H (2005) Role of the Schizosaccharomyces pombe F-Box DNA helicase in processing recombination intermediates. Mol Cell Biol 25:8074–8083

    CAS  PubMed Central  PubMed  Google Scholar 

  • Moritz M, Agard DA (2001) Gammatubulin complexes and microtubule nucleation. Curr Opin Struct Biol 11:174–181

    CAS  PubMed  Google Scholar 

  • Myung K, Datta A, Chen C, Kolodner RD (2001) SGS1, the Saccharomyces cerevisiae homologue of BLM and WRN, suppresses genome instability and homeologous recombination. Nat Genet 27:113–116

    CAS  PubMed  Google Scholar 

  • Namsaraev EA, Berg P (2000) Rad51 uses one mechanism to drive DNA strand exchange in both directions. J Biol Chem 275:3970–3976

    CAS  PubMed  Google Scholar 

  • New JH, Sugiyama T, Zaitseva E, Kowalczykowski SC (1998) Rad52 protein stimulates DNA strand exchange by Rad51 and replication protein A. Nature 391:407–410

    CAS  PubMed  Google Scholar 

  • Ogawa T, Yu X, Shinohara A, Egelman EH (1993) Similarity of the yeast RAD51 filament to the bacterial RecA filament. Science 259:1896–1899

    CAS  PubMed  Google Scholar 

  • Orren DK, Theodore S, Machwe A (2002) The Werner syndrome helicase/exonuclease (WRN) disrupts and degrades D-loops in vitro. Biochemistry 41:13483–13488

    CAS  PubMed  Google Scholar 

  • Osman F, Dixon J, Barr AR, Whitby MC (2005) The F-Box DNA helicase Fbh1 prevents Rhp51-dependent recombination without mediator proteins. Mol Cell Biol 25:8084–8096

    CAS  PubMed Central  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Papouli E, Chen SH, Davies AA, Huttner D, Krejci L, Sung P, Ulrich HD (2005) Crosstalk between SUMO and ubiquitin on PCNA is mediated by recruitment of the helicase Srs2p. Mol Cell 19:123–133

    CAS  PubMed  Google Scholar 

  • Paques F, Haber JE (1997) Two pathways for removal of nonhomologous DNA ends during double-strand break repair in Saccharomyces cerevisiae. Mol Cell Biol 17:6765–6771

    CAS  PubMed Central  PubMed  Google Scholar 

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

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pellegrini L, Venkitaraman A (2004) Emerging functions of BRCA2 in DNA recombination. Trends Biochem Sci 29:310–316

    CAS  PubMed  Google Scholar 

  • Petukhova G, Stratton S, Sung P (1998) Catalysis of homologous DNA pairing by yeast Rad51 and Rad54 proteins. Nature 393:91–94

    CAS  PubMed  Google Scholar 

  • Petukhova G, Sung P, Klein H (2000) Promotion of Rad51-dependent D-loop formation by yeast recombination factor Rdh54/Tid1. Genes Dev 14:2206–2215

    CAS  PubMed Central  PubMed  Google Scholar 

  • Petukhova G, Van Komen S, Vergano S, Klein H, Sung P (1999) Yeast Rad54 promotes Rad51-dependent homologous DNA pairing via ATP hydrolysis-driven change in DNA double helix conformation. J Biol Chem 274:29453–29462

    CAS  PubMed  Google Scholar 

  • Pfander B, Moldovan GL, Sacher M, Hoege C, Jentsch S (2005) SUMO-modified PCNA recruits Srs2 to prevent recombination during S phase. 436:428–433

    CAS  Google Scholar 

  • Pollard TD, Borisy GG (2003) Cellular motility driven by assembly and disassembly of actin filaments. Cell 112:453–465

    CAS  PubMed  Google Scholar 

  • Rattray AJ, Strathern JN (2003) Errorprone DNA polymerases: When making a mistake is the only way to get ahead. Annu Rev Genet 37:31–66

    CAS  PubMed  Google Scholar 

  • Raynard S, Bussen W, Sung P (2006) A double Holliday junction dissolvasome comprising BLM, topoisomerase III alpha, and BLAP75. J Biol Chem 281:13861–13864

    CAS  PubMed  Google Scholar 

  • Rijkers T, VandenOuweland J, Morolli B, Rolink AG, Baarends WM, VanSloun PPH, Lohman PHM, Pastink A (1998) Targeted inactivation of mouse RAD52 reduces homologous recombination but not resistance to ionizing radiation. Mol Cell Biol 18:6423–6429

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ristic D, Modesti M, van der Heijden T, van Noort J, Dekker C, Kanaar R, Wyman C (2005) Human Rad51 filaments on double and single-stranded DNA: correlating regular and irregular forms with recombination function. Nucleic Acids Res 33:3292–3302

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ristic D, Wyman C, Paulusma C, Kanaar R (2001) The architecture of the human Rad54-DNA complex provides evidence for protein translocation along DNA. Proc Natl Acad Sci USA 98:8454–8460

    CAS  PubMed Central  PubMed  Google Scholar 

  • Robison JG, Elliott J, Dixon K, Oakley GG (2004) Replication protein A and the Mre11•Rad50•Nbs1 complex colocalize and interact at sites of stalled replication forks. J Biol Chem 279:34802–34810

    CAS  PubMed  Google Scholar 

  • Rong L, Klein HL (1993) Purification and characterization of the SRS2 DNA helicase of the yeast Saccharomyces cerevisiae. J Biol Chem 268:1252–1259

    CAS  PubMed  Google Scholar 

  • San Filippo J, Chi P, Sehorn MG, Etchin J, Krejci L, Sung P (2006) Recombination mediator and Rad51 targeting activities of a human BRCA2 polypeptide. J Biol Chem 281:11649–11657

    Google Scholar 

  • Seitz EM, Haseltine CA, Kowalczykowski SC (2001) DNA recombination and repair in archaea. Adv Appl Microbiol 50:101–169

    CAS  PubMed  Google Scholar 

  • Shim KS, Schmutte C, Tombline G, Heinen CD, Fishel R (2004) hXRCC2 enhances ADP/ATP processing and strand exchange by hRAD51. J Biol Chem 279:30385–30394

    CAS  PubMed  Google Scholar 

  • Shinohara A, Ogawa H, Matsuda Y, Ushio N, Ikea K, Ogawa T (1993) Cloning of human, mouse and fission yeast recombination genes homologous to RAD51 and recA. Nat Genet 4:239–243

    CAS  PubMed  Google Scholar 

  • Shinohara A, Ogawa H, Ogawa T (1992) Rad51 protein involved in repair and recombination in S. cerevisiae is a RecA-like protein. Cell 69:457–470

    CAS  PubMed  Google Scholar 

  • Shinohara A, Ogawa T (1998) Stimulation by Rad52 of yeast Rad51-mediated recombination. Nature 391:404–407

    CAS  PubMed  Google Scholar 

  • Shinohara A, Shinohara M, Ohta T, Matsuda S, Ogawa T (1998) Rad52 forms ring structures and cooperates with RPA in single-strand annealing. Genes Cells 3:145–156

    CAS  PubMed  Google Scholar 

  • Shor E, Weinstein J, Rothstein R (2005) Genetic screen for top3 suppressors in Saccharomyces cerevisiae identifies SHU1, SHU2, PSY3 and CSM2: Four genes involved in error-free DNA repair. Genetics 169:1275–1289

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sigurdsson S, Trujillo K, Song BW, Stratton S, Sung P (2001a) Basis for avid homologous DNA strand exchange by human Rad51 and RPA. J Biol Chem 276:8798–8806

    CAS  PubMed  Google Scholar 

  • Sigurdsson S, Van Komen S, Bussen W, Schild D, Albala JS, Sung P (2001b) Mediator function of the human Rad51B-Rad51C complex in Rad51/RPA-catalyzed DNA strand exchange. Genes Dev 15:3308–3318

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sigurdsson S, Van Komen S, Petukhova G, Sung P (2002) Homologous DNA pairing by human recombination factors Rad51 and Rad54. J Biol Chem 277:42790–42794

    CAS  PubMed  Google Scholar 

  • Singleton MR, Sawaya MR, Ellenbeger T, Wigley DB (2000) Crystal structure of T7 gene 4 ring helicase indicates a mechanism for sequential hydrolysis of nucleotides. Cell 101:589–600

    CAS  PubMed  Google Scholar 

  • Singleton MR, Wentzell LM, Liu YL, West SC, Wigley DB (2002) Structure of the single-strand annealing domain of human RAD52 protein. Proc Natl Acad Sci USA 99:13492–13497

    CAS  PubMed Central  PubMed  Google Scholar 

  • Slupianek A, Schmutte C, Tombline G, Nieborowska-Skorska M, Hoser G, Nowicki MO, Pierce AJ, Fishel R, Skorski T (2001) BCR/ABL regulates mammalian RecA homologs, resulting in drug resistance. Mol Cell 8:795–806

    CAS  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 

  • Solinger JA, Heyer W-D (2001) Rad54 protein stimulates the postsynaptic phase of Rad51 protein-mediated DNA strand exchange. Proc Natl Acad Sci USA 98:8447–8453

    CAS  PubMed Central  PubMed  Google Scholar 

  • Solinger JA, Kiianitsa K, Heyer W-D (2002) Rad54, a Swi2/Snf2-like recombinational repair protein, disassembles Rad51:dsDNA filaments. Mol Cell 10:1175–1188

    CAS  PubMed  Google Scholar 

  • Solinger JA, Lutz G, Sugiyama T, Kowalczykowski SC, Heyer W-D (2001) Rad54 protein stimulates heteroduplex DNA formation in the synaptic phase of DNA strand exchange via specific interactions with the presynaptic Rad51 nucleoprotein filament. J Mol Biol 307:1207–1221

    CAS  PubMed  Google Scholar 

  • Spell RM, Jinks-Robertson S (2004) Examination of the roles of Sgs1 and Srs2 helicases in the enforcement of recombination fidelity in Saccharomyces cerevisiae. Genetics 168:1855–1865

    CAS  PubMed Central  PubMed  Google Scholar 

  • Spies M, Kowalczykowski SC (2006) The RecA binding locus of RecBCD is a general domain for recruitment of DNA strand exchange proteins. Mol Cell 21:573–580

    CAS  PubMed  Google Scholar 

  • Stasiak AZ, Larquet E, Stasiak A, Muller S, Engel A, Van Dyck E, West SC, Egelman EH (2000) The human Rad52 protein exists as a heptameric ring. Curr Biol 10:337–340

    CAS  PubMed  Google Scholar 

  • Story RM, Weber IT, Steitz TA (1992) The structure of the E. coli recA protein monomer and polymer. Nature 355:318–325

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Sugiyama T, New JH, Kowalczykowski SC (1998) DNA annealing by Rad52 Protein is stimulated by specific interaction with the complex of replication protein A and single-stranded DNA. Proc Natl Acad Sci USA 95:6049–6054

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sugiyama T, Zaitseva EM, Kowalczykowski SC (1997) A single-stranded DNA-binding protein is needed for efficient presynaptic complex formation by the Saccharomyces cerevisiae Rad51 protein. J Biol Chem 272:7940–7945

    CAS  PubMed  Google Scholar 

  • Sung P (1994) Catalysis of ATP-dependent homologous DNA pairing and strand exchange by yeast RAD51 protein. Science 265:1241–1243

    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 

  • Sung P, Krejci L, Van Komen S, Sehorn MG (2003) Rad51 recombinase and recombination mediators. J Biol Chem 278:42729–42732

    CAS  PubMed  Google Scholar 

  • Sung P, Robberson DL (1995) DNA strand exchange mediated by a RAD51-ssDNA nucleoprotein filament with polarity opposite to that of RecA. Cell 82:453–461

    CAS  PubMed  Google Scholar 

  • Sung P, Stratton SA (1996) Yeast Rad51 recombinase mediates polar DNA strand exchange in the absence of ATP hydrolysis. J Biol Chem 271:27983–27986

    CAS  PubMed  Google Scholar 

  • Swagemakers SMA, Essers J, deWit J, Hoeijmakers JHJ, Kanaar R (1998) The human Rad54 recombinational DNA repair protein is a double-stranded DNA-dependent AT-Pase. J Biol Chem 273:28292–28297

    CAS  PubMed  Google Scholar 

  • Symington LS (2002) Role of RAD52 epistasis group genes in homologous recombination and double-strand break repair. Microbiol Mol Biol Rev 66:630–670

    CAS  PubMed Central  PubMed  Google Scholar 

  • Takata M, Sasaki MS, Sonoda E, Fukushima T, Morrison C, Albala JS, Swagemakers SMA, Kanaar R, Thompson LH, Takeda S (2000) The Rad51 paralog Rad51B promotes homologous recombinational repair. Mol Cell Biol 20:6476–6482

    CAS  PubMed Central  PubMed  Google Scholar 

  • Takata M, Sasaki MS, Tachiiri S, Fukushima T, Sonoda E, Schild D, Thompson LH, Takeda S (2001) Chromosome instability and defective recombinational repair in knockout mutants of the five Rad51 paralogs. Mol Cell Biol 21:2858–2866

    CAS  PubMed Central  PubMed  Google Scholar 

  • Takizawa Y, Kinebuchi T, Kagawa W, Yokoyama S, Shibata T, Kurumizaka H (2004) Mutational analyses of the human Rad51-Tyr315 residue, a site for phosphorylation in leukaemia cells. Genes Cells 9:781–790

    CAS  PubMed  Google Scholar 

  • Tan TLR, Kanaar R, Wyman C (2003) Rad54, a Jack of all trades in homologous recombination (vol 2, pg 787, 2003). DNA Repair (Amst) 2:1293

    Google Scholar 

  • Tarsounas M, Davies D, West SC (2003) BRCA2-dependent and independent formation of RAD51 nuclear foci. Oncogene 22:1115–1123

    CAS  PubMed  Google Scholar 

  • Thacker J (2005) The RAD51 gene family, genetic instability and cancer. Cancer Lett 219:125–135

    CAS  PubMed  Google Scholar 

  • Tombline G, Fishel R (2002) Biochemical characterization of the human RAD51 protein I. ATP hydrolysis. J Biol Chem 277:14417–14425

    CAS  PubMed  Google Scholar 

  • Tombline G, Heinen CD, Shim KS, Fishel R (2002) Biochemical characterization of the human RAD51 protein — III. — Modulation of DNA binding by adenosine nucleotides. J Biol Chem 277:14434–14442

    CAS  PubMed  Google Scholar 

  • van Brabant AJ, Ye T, Sanz M, German JL, Ellis NA, Holloman WK (2000) Binding and melting of D-loops by the Bloom syndrome helicase. Biochemistry 39:14617–14625

    PubMed  Google Scholar 

  • Van Komen S, Petukhova G, Sigurdsson S, Stratton S, Sung P (2000) Superhelicitydriven homologous DNA pairing by yeast recombination factors Rad51 and Rad54. Mol Cell 6:563–572

    PubMed  Google Scholar 

  • Vassin VM, Wold MS, Borowiec JA (2004) Replication protein A (RPA) phosphorylation prevents RPA association with replication centers. Mol Cell Biol 24:1930–1943

    CAS  PubMed Central  PubMed  Google Scholar 

  • Vaze MB, Pellicioli A, Lee SE, 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 

  • West SC (2003) Molecular views of recombination proteins and their control. Nat Rev Mol Cell Biol 4:435–445

    CAS  PubMed  Google Scholar 

  • Wold MS (1997) Replication protein A: A heterotrimeric, single-stranded DNA-binding protein required for eukaryotic DNA metabolism. Annu Rev Biochem 66:61–92

    CAS  PubMed  Google Scholar 

  • Wolner B, Peterson CL (2005) ATP-dependent and ATP-independent roles for the Rad54 chromatin remodeling enzyme during recombinational repair of a DNA double strand break. J Biol Chem 280:10855–10860

    CAS  PubMed  Google Scholar 

  • Worth L, Clark S, Radman M, Modrich P (1994) Mismatch repair proteins MutS and MutL inhibit RecA-catalyzed strand transfer between diverged DNAs. Proc Natl Acad Sci USA 91:3238–3241

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wu L, Bachrati CZ, Ou JW, Xu C, Yin JH, Chang M, Wang WD, Li L, Brown GW, Hickson ID (2006) BLAP75/RMI1 promotes the BLM-dependent dissolution of homologous recombination intermediates. Proc Natl Acad Sci USA103:4068–4073

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wu L, Davies SL, Levitt NC, Hickson ID (2001) Potential role for the BLM helicase in recombinational repair via a conserved interaction with RAD51. J Biol Chem 276:19375–19381

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Wu Y, Sugiyama T, Kowalczykowski SC (2006) DNA annealing mediated by Rad52 and Rad59 proteins. J Biol Chem 281:15441–15449

    CAS  PubMed  Google Scholar 

  • Wyman C, Ristic D, Kanaar R (2004) Homologous recombinationmediated double-strand break repair. DNA Repair (Amst) 3:827–833

    CAS  Google Scholar 

  • Xu L, Marians KJ (2002) A dynamic RecA filament permits DNA polymerase-catalyzed extension of the invading strand in recombination intermediates. J Biol Chem 277:14321–14328

    CAS  PubMed  Google Scholar 

  • Yang HJ, Jeffrey PD, Miller J, Kinnucan E, Sun YT, Thoma NH, Zheng N, Chen PL, Lee WH, Pavletich NP (2002) BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA structure. Science 297:1837–1848

    CAS  PubMed  Google Scholar 

  • Yang HJ, Li QB, Fan J, Holloman WK, Pavletich NP (2005) The BRCA2 homologue Brh2 nucleates RAD51 filament formation at a dsDNA-ssDNA junction. Nature 433:653–657

    CAS  PubMed  Google Scholar 

  • Yonetani Y, Hochegger H, Sonoda E, Shinya S, Yoshikawa H, Takeda S, Yamazoe M (2005) Differential and collaborative actions of Rad51 paralog proteins in cellular response to DNA damage. Nucleic Acids Res 33:4544–4552

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yu X, Jacobs SA, West SC, Ogawa T, Egelman EH (2001) Domain structure and dynamics in the helical filaments formed by RecA and Rad51 on DNA. Proc Natl Acad Sci USA 98:8419–8425

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yuan ZM, Huang YY, Ishiko T, Nakada S, Utsugisawa T, Kharbanda S, Wang R, Sung P, Shinohara A, Weichselbaum R, Kufe D (1998) Regulation of Rad51 function by c-Abl in response to DNA damage. J Biol Chem 273:3799–3802

    CAS  PubMed  Google Scholar 

  • Zaitseva EM, Zaitsev EN, Kowalczykowski SC (1999) The DNA binding properties of Saccharomyces cerevisiae Rad51 protein. J Biol Chem 274:2907–2915

    CAS  PubMed  Google Scholar 

  • Zhou BBS, Elledge SJ (2000) The DNA damage response: putting checkpoints in perspective. Nature 408:433–439

    CAS  PubMed  Google Scholar 

  • Zigmond SH (2004) Formininduced nucleation of actin filaments. Curr Opin Cell Biol 16:99–105

    CAS  PubMed  Google Scholar 

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Heyer, WD. (2007). Biochemistry of eukaryotic homologous recombination. 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_4

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