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Site-directed insertion of transgenes pp 91–120Cite as

Homologous Recombination in Mammals

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Part of the book series: Topics in Current Genetics ((TCG,volume 23))

Abstract

Homologous recombination (HR) is a fundamental process that is conserved in all species and is essential for maintaining genome stability while facilitating genetic diversity but avoiding genetic instability. As such, HR is involved in numerous fundamental biological processes, controlling a balance of genetic stability/diversity instability. This chapter summarizes the different models of recombination in mammals and then presents the following molecular steps of HR: recognition of damage, chromatin remodeling, DNA single-strand resection, strand invasion and resolution of Holliday junctions. HR is a process involved in DNA repair (notably double-strand breaks), the tolerance of damages and the reactivation of stalled replication forks; it is essential for the maintenance of genome stability. Conversely, an excess of HR (for example, between dispersed repeated sequences in the genome) can lead to genetic instability. In this context, the regulation of HR restricting it to S-phase is a factor in genetic stability. Deregulation of HR (causing a defect or an excess) is often found in tumor cells and tumor predisposition situations, illustrating the need for precise control of balance in HR. Knowledge of the molecular mechanisms of HR is also of interest in applications because it may provide strategies for the optimization of targeted in gene replacement.

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References

  • Amor M, Parker KL, Globerman H, New MI, White PC (1988) Mutation in the CYP21B gene (Ile-172––Asn) causes steroid 21 – hydroxylase deficiency. Proc Natl Acad Sci USA 85:1600–1604

    Article  CAS  Google Scholar 

  • Arnheim N (1983) Concerted evolution of multigene families. In: Koehn RK, Nei M (eds) Evolution of genes and proteins. Sinauer, Sunderland, pp 38–61

    Google Scholar 

  • Aten JA, Stap J, Krawczyk PM, van Oven CH, Hoebe RA, Essers J, Kanaar R (2004) Dynamics of DNA double-strand breaks revealed by clustering of damaged chromosome domains. Science 303:92–95

    Article  CAS  Google Scholar 

  • Bartkova J, Horejsi Z, Koed K, Kramer A, Tort F, Zieger K, Guldberg P, Sehested M, Nesland JM, Lukas C, Orntoft T, Lukas J, Bartek J (2005) DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature 434:864–870

    Article  CAS  Google Scholar 

  • Bertrand P, Lambert S, Joubert C, Lopez BS (2003) Overexpression of mammalian Rad51 does not stimulate tumorigenesis while a dominant-negative Rad51 affects centrosome fragmentation, ploidy and stimulates tumorigenesis, in p53-defective CHO cells. Oncogene 22:7587–7592

    Article  CAS  Google Scholar 

  • Bertrand P, Saintigny Y, Lopez BS (2004) p53’s double life: transactivation-independent repression of homologous recombination. Trends Genet 20:235–243

    Article  CAS  Google Scholar 

  • Boddy MN, Gaillard PH, McDonald WH, Shanahan P, Yates JR 3rd, Russell P (2001) Mus81-Eme1 are essential components of a Holliday junction resolvase. Cell 107:537–548

    Article  CAS  Google Scholar 

  • Bolderson E, Tomimatsu N, Richard DJ, Boucher D, Kumar R, Pandita TK, Burma S, Khanna KK (2010) Phosphorylation of Exo1 modulates homologous recombination repair of DNA double-strand breaks. Nucleic Acids Res 38:1821–1831

    Article  CAS  Google Scholar 

  • Botuyan MV, Lee J, Ward IM, Kim JE, Thompson JR, Chen J, Mer G (2006) Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair. Cell 127:1361–1373

    Article  CAS  Google Scholar 

  • Bouwman P, Aly A, Escandell JM, Pieterse M, Bartkova J, van der Gulden H, Hiddingh S, Thanasoula M, Kulkarni A, Yang Q, Haffty BG, Tommiska J, Blomqvist C, Drapkin R, Adams DJ, Nevanlinna H, Bartek J, Tarsounas M, Ganesan S, Jonkers J (2010) 53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers. Nat Struct Mol Biol 17:688–695

    Article  CAS  Google Scholar 

  • Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, Kyle S, Meuth M, Curtin NJ, Helleday T (2005) Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434:913–917

    Article  CAS  Google Scholar 

  • Buard J, de Massy B (2007) Playing hide and seek with mammalian meiotic crossover hotspots. Trends Genet 23:301–309

    Article  CAS  Google Scholar 

  • Bunting SF, Callen E, Wong N, Chen HT, Polato F, Gunn A, Bothmer A, Feldhahn N, Fernandez-Capetillo O, Cao L, Xu X, Deng CX, Finkel T, Nussenzweig M, Stark JM, Nussenzweig A (2010) 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks. Cell 141:243–254

    Article  CAS  Google Scholar 

  • Burma S, Chen BP, Murphy M, Kurimasa A, Chen DJ (2001) ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J Biol Chem 276:42462–42467

    Article  CAS  Google Scholar 

  • Cao L, Xu X, Bunting SF, Liu J, Wang RH, Cao LL, Wu JJ, Peng TN, Chen J, Nussenzweig A, Deng CX, Finkel T (2009) A selective requirement for 53BP1 in the biological response to genomic instability induced by Brca1 deficiency. Mol Cell 35:534–541

    Article  CAS  Google Scholar 

  • Celeste A, Fernandez-Capetillo O, Kruhlak MJ, Pilch DR, Staudt DW, Lee A, Bonner RF, Bonner WM, Nussenzweig A (2003) Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks. Nat Cell Biol 5:675–679

    Article  CAS  Google Scholar 

  • Chailleux C, Tyteca S, Papin C, Boudsocq F, Puget N, Courilleau C, Grigoriev M, Canitrot Y, Trouche D (2010) Physical interaction between the histone acetyl transferase Tip60 and the DNA double-strand breaks sensor MRN complex. Biochem J 426:365–371

    Article  CAS  Google Scholar 

  • Chapman JR, Jackson SP (2008) Phospho-dependent interactions between NBS1 and MDC1 mediate chromatin retention of the MRN complex at sites of DNA damage. EMBO Rep 9:795–801

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Chen JM, Cooper DN, Chuzhanova N, Ferec C, Patrinos GP (2007) Gene conversion: mechanisms, evolution and human disease. Nat Rev Genet 8:762–775

    Article  CAS  Google Scholar 

  • Chen L, Nievera CJ, Lee AY, Wu X (2008) Cell cycle-dependent complex formation of BRCA1.CtIP.MRN is important for DNA double-strand break repair. J Biol Chem 283:7713–7720

    Article  CAS  Google Scholar 

  • Cheong N, Wang X, Wang Y, Iliakis G (1994) Loss of S-phase-dependent radioresistance in irs-1 cells exposed to X-rays. Mutat Res 314:77–85

    Article  CAS  Google Scholar 

  • Chowdhury D, Keogh MC, Ishii H, Peterson CL, Buratowski S, Lieberman J (2005) gamma-H2AX dephosphorylation by protein phosphatase 2A facilitates DNA double-strand break repair. Mol Cell 20:801–809

    Article  CAS  Google Scholar 

  • Chowdhury D, Xu X, Zhong X, Ahmed F, Zhong J, Liao J, Dykxhoorn DM, Weinstock DM, Pfeifer GP, Lieberman J (2008) A PP4-phosphatase complex dephosphorylates gamma-H2AX generated during DNA replication. Mol Cell 31:33–46

    Article  CAS  Google Scholar 

  • Chu WK, Hickson ID (2009) RecQ helicases: multifunctional genome caretakers. Nat Rev Cancer 9:644–654

    Article  CAS  Google Scholar 

  • Coleman KA, Greenberg RA (2011) The BRCA1-RAP80 complex regulates DNA repair mechanism utilization by restricting end resection. J Biol Chem 286:13669–13680

    Article  CAS  Google Scholar 

  • Couedel C, Mills KD, Barchi M, Shen L, Olshen A, Johnson RD, Nussenzweig A, Essers J, Kanaar R, Li GC, Alt FW, Jasin M (2004) Collaboration of homologous recombination and nonhomologous end-joining factors for the survival and integrity of mice and cells. Genes Dev 18:1293–1304

    Article  CAS  Google Scholar 

  • Creighton HB, McClintock B (1931) A correlation of cytological and genetical crossing-over in Zea mays. Proc Natl Acad Sci USA 17:492–497

    Article  CAS  Google Scholar 

  • Daboussi F, Thacker J, Lopez BS (2005) Genetic interactions between RAD51 and its paralogues for centrosome fragmentation and ploidy control, independently of the sensitivity to genotoxic stresses. Oncogene 24:3691–3696

    Article  CAS  Google Scholar 

  • Daboussi F, Courbet S, Benhamou S, Kannouche P, Zdzienicka MZ, Debatisse M, Lopez BS (2008) A homologous recombination defect affects replication-fork progression in mammalian cells. J Cell Sci 121:162–166

    Article  CAS  Google Scholar 

  • Dendouga N, Gao H, Moechars D, Janicot M, Vialard J, McGowan CH (2005) Disruption of murine Mus81 increases genomic instability and DNA damage sensitivity but does not promote tumorigenesis. Mol Cell Biol 25:7569–7579

    Article  CAS  Google Scholar 

  • Deng CX (2002) Roles of BRCA1 in centrosome duplication. Oncogene 21:6222–6227

    Article  CAS  Google Scholar 

  • Deutsch E, Dugray A, AbdulKarim B, Marangoni E, Maggiorella L, Vaganay S, M’Kacher R, Rasy SD, Eschwege F, Vainchenker W, Turhan AG, Bourhis J (2001) BCR-ABL down-regulates the DNA repair protein DNA-PKcs. Blood 97:2084–2090

    Article  CAS  Google Scholar 

  • Doil C, Mailand N, Bekker-Jensen S, Menard P, Larsen DH, Pepperkok R, Ellenberg J, Panier S, Durocher D, Bartek J, Lukas J, Lukas C (2009) RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins. Cell 136:435–446

    Article  CAS  Google Scholar 

  • Downs JA, Allard S, Jobin-Robitaille O, Javaheri A, Auger A, Bouchard N, Kron SJ, Jackson SP, Cote J (2004) Binding of chromatin-modifying activities to phosphorylated histone H2A at DNA damage sites. Mol Cell 16:979–990

    Article  CAS  Google Scholar 

  • Dresser ME, Ewing DJ, Conrad MN, Dominguez AM, Barstead R, Jiang H, Kodadek T (1997) DMC1 functions in a Saccharomyces cerevisiae meiotic pathway that is largely independent of the RAD51 pathway. Genetics 147:533–544

    CAS  Google Scholar 

  • Dunham MA, Neumann AA, Fasching CL, Reddel RR (2000) Telomere maintenance by recombination in human cells. Nat Genet 26:447–450

    Article  CAS  Google Scholar 

  • Eid W, Steger M, El-Shemerly M, Ferretti LP, Pena-Diaz J, Konig C, Valtorta E, Sartori AA, Ferrari S (2010) DNA end resection by CtIP and exonuclease 1 prevents genomic instability. EMBO Rep 11:962–968

    Article  CAS  Google Scholar 

  • Eladad S, Ye TZ, Hu P, Leversha M, Beresten S, Matunis MJ, Ellis NA (2005) Intra-nuclear trafficking of the BLM helicase to DNA damage-induced foci is regulated by SUMO modification. Hum Mol Genet 14:1351–1365

    Article  CAS  Google Scholar 

  • Elborough KM, West SC (1990) Resolution of synthetic Holliday junctions in DNA by an endonuclease activity from calf thymus. EMBO J 9:2931–2936

    CAS  Google Scholar 

  • Erkko H, Pylkas K, Karppinen SM, Winqvist R (2008) Germline alterations in the CLSPN gene in breast cancer families. Cancer Lett 261:93–97

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, Santarosa M, Dillon KJ, Hickson I, Knights C, Martin NM, Jackson SP, Smith GC, Ashworth A (2005) Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434:917–921

    Article  CAS  Google Scholar 

  • Fekairi S, Scaglione S, Chahwan C, Taylor ER, Tissier A, Coulon S, Dong MQ, Ruse C, Yates JR, Russell P, Fuchs RP, McGowan CH, Gaillard PH (2009) Human SLX4 is a Holliday junction resolvase subunit that binds multiple DNA repair/recombination endonucleases. Cell 138:78–89

    Article  CAS  Google Scholar 

  • Fillingham J, Keogh MC, Krogan NJ (2006) GammaH2AX and its role in DNA double-strand break repair. Biochem Cell Biol 84:568–577

    Article  CAS  Google Scholar 

  • Galanty Y, Belotserkovskaya R, Coates J, Polo S, Miller KM, Jackson SP (2009) Mammalian SUMO E3-ligases PIAS1 and PIAS4 promote responses to DNA double-strand breaks. Nature 462:935–939

    Article  CAS  Google Scholar 

  • Gangloff S, Soustelle C, Fabre F (2000) Homologous recombination is responsible for cell death in the absence of the Sgs1 and Srs2 helicases. Nat Genet 25:192–194

    Article  CAS  Google Scholar 

  • Gorgoulis VG, Vassiliou LV, Karakaidos P, Zacharatos P, Kotsinas A, Liloglou T, Venere M, Ditullio RAJ, Kastrinakis NG, Levy B, Kletsas D, Yoneta A, Herlyn M, Kittas C, Halazonetis TD (2005) Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions. Nature 434:907–913

    Article  CAS  Google Scholar 

  • Gravel S, Chapman JR, Magill C, Jackson SP (2008) DNA helicases Sgs1 and BLM promote DNA double-strand break resection. Genes Dev 22:2767–2772

    Article  CAS  Google Scholar 

  • Griffin CS, Simpson PJ, Wilson CR, Thacker J (2000) Mammalian recombination-repair genes XRCC2 and XRCC3 promote correct chromosome segregation. Nat Cell Biol 2:757–761

    Article  CAS  Google Scholar 

  • Guirouilh-Barbat J, Huck S, Lopez BS (2008) S-phase progression stimulates both the mutagenic KU-independent pathway and mutagenic processing of KU-dependent intermediates, for nonhomologous end joining. Oncogene 27:1726–1736

    Article  CAS  Google Scholar 

  • Guirouilh-Barbat J, Wilhelm T, Lopez BS (2010) AKT1/BRCA1 in the control of homologous recombination and genetic stability: the missing link between hereditary and sporadic breast cancers. Oncotarget 1:691–699

    Google Scholar 

  • Haldane JB (1919) The combination of linkage values and the calculation of distance between the loci of linked factors. J Genet 8:299–309

    Article  Google Scholar 

  • Haldane JB, Lea DE (1947) A mathematical theory of chromosomal rearrangements. J Genet 48:1–10

    Article  CAS  Google Scholar 

  • Hinz JM, Yamada NA, Salazar EP, Tebbs RS, Thompson LH (2005) Influence of double-strand-break repair pathways on radiosensitivity throughout the cell cycle in CHO cells. DNA Repair (Amst) 4:782–792

    Article  CAS  Google Scholar 

  • Hiramoto T, Nakanishi T, Sumiyoshi T, Fukuda T, Matsuura S, Tauchi H, Komatsu K, Shibasaki Y, Inui H, Watatani M, Yasutomi M, Sumii K, Kajiyama G, Kamada N, Miyagawa K, Kamiya K (1999) Mutations of a novel human RAD54 homologue, RAD54B, in primary cancer. Oncogene 18:3422–3426

    Article  CAS  Google Scholar 

  • Holliday R (1964) A mechanism for gene conversion in fungi. Genet Res 5:282–306

    Article  Google Scholar 

  • Holthausen JT, Wyman C, Kanaar R (2010) Regulation of DNA strand exchange in homologous recombination. DNA Repair (Amst) 9:1264–1272

    Article  CAS  Google Scholar 

  • Huertas P (2010) DNA resection in eukaryotes: deciding how to fix the break. Nat Struct Mol Biol 17:11–16

    Article  CAS  Google Scholar 

  • Huyen Y, Zgheib O, Ditullio RA Jr, Gorgoulis VG, Zacharatos P, Petty TJ, Sheston EA, Mellert HS, Stavridi ES, Halazonetis TD (2004) Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks. Nature 432:406–411

    Article  CAS  Google Scholar 

  • Hyrien O (2000) Mechanisms and consequences of replication fork arrest. Biochimie 82:5–17

    Article  CAS  Google Scholar 

  • Ikura T, Tashiro S, Kakino A, Shima H, Jacob N, Amunugama R, Yoder K, Izumi S, Kuraoka I, Tanaka K, Kimura H, Ikura M, Nishikubo S, Ito T, Muto A, Miyagawa K, Takeda S, Fishel R, Igarashi K, Kamiya K (2007) DNA damage-dependent acetylation and ubiquitination of H2AX enhances chromatin dynamics. Mol Cell Biol 27:7028–7040

    Article  CAS  Google Scholar 

  • Ip SC, Rass U, Blanco MG, Flynn HR, Skehel JM, West SC (2008) Identification of Holliday junction resolvases from humans and yeast. Nature 456:357–361

    Article  CAS  Google Scholar 

  • Johnson RD, Jasin M (2000) Sister chromatid gene conversion is a prominent double-strand break repair pathway in mammalian cells. EMBO J 19:3398–3407

    Article  CAS  Google Scholar 

  • Kaidi A, Weinert BT, Choudhary C, Jackson SP (2010) Human SIRT6 promotes DNA end resection through CtIP deacetylation. Science 329:1348–1353

    Article  CAS  Google Scholar 

  • Kim JS, Krasieva TB, Kurumizaka H, Chen DJ, Taylor AM, Yokomori K (2005) Independent and sequential recruitment of NHEJ and HR factors to DNA damage sites in mammalian cells. J Cell Biol 170:341–347

    Article  CAS  Google Scholar 

  • Kim H, Chen J, Yu X (2007) Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage response. Science 316:1202–1205

    Article  CAS  Google Scholar 

  • Kim Y, Lach FP, Desetty R, Hanenberg H, Auerbach AD, Smogorzewska A (2011) Mutations of the SLX4 gene in Fanconi anemia. Nat Genet 43:142–146

    Article  CAS  Google Scholar 

  • Kimura H, Takizawa N, Allemand E, Hori T, Iborra FJ, Nozaki N, Muraki M, Hagiwara M, Krainer AR, Fukagawa T, Okawa K (2006) A novel histone exchange factor, protein phosphatase 2Cgamma, mediates the exchange and dephosphorylation of H2A-H2B. J Cell Biol 175:389–400

    Article  CAS  Google Scholar 

  • Kinner A, Wu W, Staudt C, Iliakis G (2008) Gamma-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin. Nucleic Acids Res 36:5678–5694

    Article  CAS  Google Scholar 

  • Kleckner N (1996) Meiosis: how could it work? Proc Natl Acad Sci USA 93:8167–8174

    Article  CAS  Google Scholar 

  • Klein HL (1997) RDH54, a RAD54 homologue in Saccharomyces cerevisiae, is required for mitotic diploid-specific recombination and repair and for meiosis. Genetics 147:1533–1543

    CAS  Google Scholar 

  • Kourilsky P (1983) Genetic exchanges between partially homologous nucleotide sequences: possible implications for multigene families. Biochimie 65:85–93

    Article  CAS  Google Scholar 

  • Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705

    Article  CAS  Google Scholar 

  • Kovalenko OV, Plug AW, Haaf T, Gonda DK, Ashley T, Ward DC, Radding CM, Golub EI (1996) Mammalian ubiquitin-conjugating enzyme Ubc9 interacts with Rad51 recombination protein and localizes in synaptonemal complexes. Proc Natl Acad Sci USA 93:2958–2963

    Article  CAS  Google Scholar 

  • Kraakman-van der Zwet M, Overkamp WJ, van Lange RE, Essers J, van Duijn-Goedhart A, Wiggers I, Swaminathan S, van Buul PP, Errami A, Tan RT, Jaspers NG, Sharan SK, Kanaar R, Zdzienicka MZ (2002) Brca2 (XRCC11) deficiency results in radioresistant DNA synthesis and a higher frequency of spontaneous deletions. Mol Cell Biol 22:669–679

    Article  CAS  Google Scholar 

  • Kricker MC, Drake JW, Radman M (1992) Duplication-targeted DNA methylation and mutagenesis in the evolution of eukaryotic chromosomes. Proc Natl Acad Sci USA 89:1075–1079

    Article  CAS  Google Scholar 

  • Lahkim Bennani-Belhaj K, Rouzeau S, Buhagiar-Labarchede G, Chabosseau P, Onclercq-Delic R, Bayart E, Cordelieres F, Couturier J, Amor-Gueret M (2010) The Bloom syndrome protein limits the lethality associated with RAD51 deficiency. Mol Cancer Res 8:385–394

    Article  CAS  Google Scholar 

  • Lambert S, Lopez BS (2002) Inactivation of the RAD51 recombination pathway stimulates UV-induced mutagenesis in mammalian cells. Oncogene 21:4065–4069

    Article  CAS  Google Scholar 

  • Laulier C, Barascu A, Guirouilh-Barbat J, Pennarun G, Le Chalony C, Chevalier F, Palierne G, Bertrand P, Verbavatz JM, Lopez BS (2011a) Bcl-2 inhibits nuclear homologous recombination by localizing BRCA1 to the endomembranes. Cancer Res 71:3590–3602

    Article  CAS  Google Scholar 

  • Laulier C, Cheng A, Stark JM (2011b) The relative efficiency of homology-directed repair has distinct effects on proper anaphase chromosome separation. Nucleic Acids Res 39:5935–5944

    Article  CAS  Google Scholar 

  • Lederberg J, Tatum EL (1946) Gene recombination in Escherichia coli. Nature 158:558

    Article  CAS  Google Scholar 

  • Lee MS, Edwards RA, Thede GL, Glover JN (2005) Structure of the BRCT repeat domain of MDC1 and its specificity for the free COOH-terminal end of the gamma-H2AX histone tail. J Biol Chem 280:32053–32056

    Article  CAS  Google Scholar 

  • Li W, Hesabi B, Babbo A, Pacione C, Liu J, Chen DJ, Nickoloff JA, Shen Z (2000) Regulation of double-strand break-induced mammalian homologous recombination by UBL1, a RAD51-interacting protein. Nucleic Acids Res 28:1145–1153

    Article  CAS  Google Scholar 

  • Liao D (1999) Concerted evolution: molecular mechanism and biological implications. Am J Hum Genet 64:24–30

    Article  CAS  Google Scholar 

  • Limbo O, Chahwan C, Yamada Y, de Bruin RA, Wittenberg C, Russell P (2007) Ctp1 is a cell-cycle-regulated protein that functions with Mre11 complex to control double-strand break repair by homologous recombination. Mol Cell 28:134–146

    Article  CAS  Google Scholar 

  • Lin FL, Sperle K, Sternberg N (1984) Homologous recombination in mouse L cells. Cold Spring Harb Symp Quant Biol 49:139–149

    Article  CAS  Google Scholar 

  • Liskay RM, Stachelek JL (1983) Evidence for intrachromosomal gene conversion in cultured mouse cells. Cell 35:157–165

    Article  CAS  Google Scholar 

  • Liskay RM, Stachelek JL, Letsou A (1984) Homologous recombination between repeated chromosomal sequences in mouse cells. Cold Spring Harb Symp Quant Biol 49:183–189

    Article  CAS  Google Scholar 

  • Liskay RM, Letsou A, Stachelek JL (1987) Homology requirement for efficient gene conversion between duplicated chromosomal sequences in mammalian cells. Genetics 115:161–167

    CAS  Google Scholar 

  • Lopez BS, Corteggiani E, Bertrand-Mercat P, Coppey J (1992) Directional recombination is initiated at a double strand break in human nuclear extracts. Nucleic Acids Res 20:501–506

    Article  CAS  Google Scholar 

  • Lusser A, Kadonaga JT (2003) Chromatin remodeling by ATP-dependent molecular machines. Bioessays 25:1192–1200

    Article  CAS  Google Scholar 

  • Mailand N, Bekker-Jensen S, Faustrup H, Melander F, Bartek J, Lukas C, Lukas J (2007) RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell 131:887–900

    Article  CAS  Google Scholar 

  • Marmorstein R, Berger SL (2001) Structure and function of bromodomains in chromatin-regulating complexes. Gene 272:1–9

    Article  CAS  Google Scholar 

  • Matulova P, Marini V, Burgess RC, Sisakova A, Kwon Y, Rothstein R, Sung P, Krejci L (2009) Cooperativity of Mus81.Mms4 with Rad54 in the resolution of recombination and replication intermediates. J Biol Chem 284:7733–7745

    Article  CAS  Google Scholar 

  • Mazina OM, Mazin AV (2008) Human Rad54 protein stimulates human Mus81-Eme1 endonuclease. Proc Natl Acad Sci USA 105:18249–18254

    Article  CAS  Google Scholar 

  • Melander F, Bekker-Jensen S, Falck J, Bartek J, Mailand N, Lukas J (2008) Phosphorylation of SDT repeats in the MDC1 N terminus triggers retention of NBS1 at the DNA damage-modified chromatin. J Cell Biol 181:213–226

    Article  CAS  Google Scholar 

  • Mills KD, Ferguson DO, Essers J, Eckersdorff M, Kanaar R, Alt FW (2004) Rad54 and DNA Ligase IV cooperate to maintain mammalian chromatid stability. Genes Dev 18:1283–1292

    Article  CAS  Google Scholar 

  • Mimitou EP, Symington LS (2009a) Nucleases and helicases take center stage in homologous recombination. Trends Biochem Sci 34:264–272

    Article  CAS  Google Scholar 

  • Mimitou EP, Symington LS (2009b) DNA end resection: many nucleases make light work. DNA Repair (Amst) 8:983–995

    Article  CAS  Google Scholar 

  • Morris JR, Boutell C, Keppler M, Densham R, Weekes D, Alamshah A, Butler L, Galanty Y, Pangon L, Kiuchi T, Ng T, Solomon E (2009) The SUMO modification pathway is involved in the BRCA1 response to genotoxic stress. Nature 462:886–890

    Article  CAS  Google Scholar 

  • Morrison AJ, Highland J, Krogan NJ, Arbel-Eden A, Greenblatt JF, Haber JE, Shen X (2004) INO80 and gamma-H2AX interaction links ATP-dependent chromatin remodeling to DNA damage repair. Cell 119:767–775

    Article  CAS  Google Scholar 

  • Moynahan ME, Chiu JW, Koller BH, Jasin M (1999) Brca1 controls homology-directed DNA repair. Mol Cell 4:511–518

    Article  CAS  Google Scholar 

  • Moynahan ME, Pierce AJ, Jasin M (2001) BRCA2 is required for homology-directed repair of chromosomal breaks. Mol Cell 7:263–272

    Article  CAS  Google Scholar 

  • Munoz IM, Hain K, Declais AC, Gardiner M, Toh GW, Sanchez-Pulido L, Heuckmann JM, Toth R, Macartney T, Eppink B, Kanaar R, Ponting CP, Lilley DM, Rouse J (2009) Coordination of structure-specific nucleases by human SLX4/BTBD12 is required for DNA repair. Mol Cell 35:116–127

    Article  CAS  Google Scholar 

  • Nakanishi K, Cavallo F, Perrouault L, Giovannangeli C, Moynahan ME, Barchi M, Brunet E, Jasin M (2011) Homology-directed Fanconi anemia pathway cross-link repair is dependent on DNA replication. Nat Struct Mol Biol 18:500–503

    Article  CAS  Google Scholar 

  • Nimonkar AV, Ozsoy AZ, Genschel J, Modrich P, Kowalczykowski SC (2008) Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair. Proc Natl Acad Sci USA 105:16906–16911

    Article  CAS  Google Scholar 

  • Osley MA, Tsukuda T, Nickoloff JA (2007) ATP-dependent chromatin remodeling factors and DNA damage repair. Mutat Res 618:65–80

    Article  CAS  Google Scholar 

  • Ouyang KJ, Woo LL, Zhu J, Huo D, Matunis MJ, Ellis NA (2009) SUMO modification regulates BLM and RAD51 interaction at damaged replication forks. PLoS Biol 7:e1000252

    Article  CAS  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  Google Scholar 

  • Park JH, Park EJ, Lee HS, Kim SJ, Hur SK, Imbalzano AN, Kwon J (2006) Mammalian SWI/SNF complexes facilitate DNA double-strand break repair by promoting gamma-H2AX induction. EMBO J 25:3986–3997

    Article  CAS  Google Scholar 

  • Paull TT, Gellert M (2000) A mechanistic basis for Mre11-directed DNA joining at microhomologies. Proc Natl Acad Sci USA 97:6409–6414

    Article  CAS  Google Scholar 

  • Petermann E, Orta ML, Issaeva N, Schultz N, Helleday T (2010) Hydroxyurea-stalled replication forks become progressively inactivated and require two different RAD51-mediated pathways for restart and repair. Mol Cell 37:492–502

    Article  CAS  Google Scholar 

  • Plo I, Lopez B (2009) AKT1 represses gene conversion induced by different genotoxic stresses and induces supernumerary centrosomes and aneuploidy in hamster ovary cells. Oncogene 28:2231–2237

    Article  CAS  Google Scholar 

  • Plo I, Laulier C, Gauthier L, Lebrun F, Calvo F, Lopez BS (2008) AKT1 inhibits homologous recombination by inducing cytoplasmic retention of BRCA1 and RAD51. Cancer Res 68:9404–9412

    Article  CAS  Google Scholar 

  • Pollard KJ, Peterson CL (1998) Chromatin remodeling: a marriage between two families? Bioessays 20:771–780

    Article  CAS  Google Scholar 

  • Purandare SM, Patel PI (1997) Recombination hot spots and human disease. Genome Res 7:773–786

    CAS  Google Scholar 

  • Richardson C, Jasin M (2000) Coupled homologous and nonhomologous repair of a double-strand break preserves genomic integrity in mammalian cells. Mol Cell Biol 20:9068–9075

    Article  CAS  Google Scholar 

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

    CAS  Google Scholar 

  • Rogakou EP, Boon C, Redon C, Bonner WM (1999) Megabase chromatin domains involved in DNA double-strand breaks in vivo. J Cell Biol 146:905–916

    Article  CAS  Google Scholar 

  • Rossi MJ, Mazin AV (2008) Rad51 protein stimulates the branch migration activity of Rad54 protein. J Biol Chem 283:24698–24706

    Article  CAS  Google Scholar 

  • Rothkamm K, Kruger I, Thompson LH, Lobrich M (2003) Pathways of DNA double-strand break repair during the mammalian cell cycle. Mol Cell Biol 23:5706–5715

    Article  CAS  Google Scholar 

  • Rubnitz J, Subramani S (1984) The minimum amount of homology required for homologous recombination in mammalian cells. Mol Cell Biol 4:2253–2258

    CAS  Google Scholar 

  • Saintigny Y, Delacote F, Vares G, Petitot F, Lambert S, Averbeck D, Lopez BS (2001) Characterization of homologous recombination induced by replication inhibition in mammalian cells. EMBO J 20:3861–3870

    Article  CAS  Google Scholar 

  • Saintigny Y, Delacote F, Boucher D, Averbeck D, Lopez BS (2007) XRCC4 in G1 suppresses homologous recombination in S/G2, in G1 checkpoint-defective cells. Oncogene 26:2769–2780

    Article  CAS  Google Scholar 

  • Saleh-Gohari N, Helleday T (2004) Conservative homologous recombination preferentially repairs DNA double-strand breaks in the S phase of the cell cycle in human cells. Nucleic Acids Res 32:3683–3688

    Article  CAS  Google Scholar 

  • Sartori AA, Lukas C, Coates J, Mistrik M, Fu S, Bartek J, Baer R, Lukas J, Jackson SP (2007) Human CtIP promotes DNA end resection. Nature 450:509–514

    Article  CAS  Google Scholar 

  • Sedelnikova OA, Pilch DR, Redon C, Bonner WM (2003) Histone H2AX in DNA damage and repair. Cancer Biol Ther 2:233–235

    CAS  Google Scholar 

  • Shen Z, Pardington-Purtymun PE, Comeaux JC, Moyzis RK, Chen DJ (1996a) Associations of UBE2I with RAD52, UBL1, p53, and RAD51 proteins in a yeast two-hybrid system. Genomics 37:183–186

    Article  CAS  Google Scholar 

  • Shen Z, Pardington-Purtymun PE, Comeaux JC, Moyzis RK, Chen DJ (1996b) UBL1, a human ubiquitin-like protein associating with human RAD51/RAD52 proteins. Genomics 36:271–279

    Article  CAS  Google Scholar 

  • Shen WH, Balajee AS, Wang J, Wu H, Eng C, Pandolfi PP, Yin Y (2007) Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell 128:157–170

    Article  CAS  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

    Article  CAS  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

    Article  CAS  Google Scholar 

  • Sobhian B, Shao G, Lilli DR, Culhane AC, Moreau LA, Xia B, Livingston DM, Greenberg RA (2007) RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage sites. Science 316:1198–1202

    Article  CAS  Google Scholar 

  • Sorensen CS, Hansen LT, Dziegielewski J, Syljuasen RG, Lundin C, Bartek J, Helleday T (2005) The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous recombination repair. Nat Cell Biol 7:195–201

    Article  CAS  Google Scholar 

  • Stewart GS (2009) Solving the RIDDLE of 53BP1 recruitment to sites of damage. Cell Cycle 8:1532–1538

    Article  CAS  Google Scholar 

  • Stewart GS, Panier S, Townsend K, Al-Hakim AK, Kolas NK, Miller ES, Nakada S, Ylanko J, Olivarius S, Mendez M, Oldreive C, Wildenhain J, Tagliaferro A, Pelletier L, Taubenheim N, Durandy A, Byrd PJ, Stankovic T, Taylor AM, Durocher D (2009) The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage. Cell 136:420–434

    Article  CAS  Google Scholar 

  • Stiff T, O’Driscoll M, Rief N, Iwabuchi K, Lobrich M, Jeggo PA (2004) ATM and DNA-PK function redundantly to phosphorylate H2AX after exposure to ionizing radiation. Cancer Res 64:2390–2396

    Article  CAS  Google Scholar 

  • Strahl BD, Allis CD (2000) The language of covalent histone modifications. Nature 403:41–45

    Article  CAS  Google Scholar 

  • Stucki M, Clapperton JA, Mohammad D, Yaffe MB, Smerdon SJ, Jackson SP (2005) MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks. Cell 123:1213–1226

    Article  CAS  Google Scholar 

  • Sun M, Wang G, Paciga JE, Feldman RI, Yuan ZQ, Ma XL, Shelley SA, Jove R, Tsichlis PN, Nicosia SV, Cheng JQ (2001) AKT1/PKBalpha kinase is frequently elevated in human cancers and its constitutive activation is required for oncogenic transformation in NIH3T3 cells. Am J Pathol 159:431–437

    Article  CAS  Google Scholar 

  • Svendsen JM, Smogorzewska A, Sowa ME, O’Connell BC, Gygi SP, Elledge SJ, Harper JW (2009) Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair. Cell 138:63–77

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Takata M, Sasaki MS, Sonoda E, Morrison C, Hashimoto M, Utsumi H, Yamaguchi-Iwai Y, Shinohara A, Takeda S (1998) Homologous recombination and non-homologous end-joining pathways of DNA double-strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells. EMBO J 17:5497–5508

    Article  CAS  Google Scholar 

  • Tambini CE, George AM, Rommens JM, Tsui LC, Scherer SW, Thacker J (1997) The XRCC2 DNA repair gene: identification of a positional candidate. Genomics 41:84–92

    Article  CAS  Google Scholar 

  • van Attikum H, Gasser SM (2005) ATP-dependent chromatin remodeling and DNA double-strand break repair. Cell Cycle 4:1011–1014

    Article  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

    Article  Google Scholar 

  • Walsh T, King MC (2007) Ten genes for inherited breast cancer. Cancer Cell 11:103–105

    Article  CAS  Google Scholar 

  • Wang B, Elledge SJ (2007) Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage. Proc Natl Acad Sci USA 104:20759–20763

    Article  CAS  Google Scholar 

  • Ward IM, Chen J (2001) Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress. J Biol Chem 276:47759–47762

    Article  CAS  Google Scholar 

  • Ward IM, Minn K, Jorda KG, Chen J (2003) Accumulation of checkpoint protein 53BP1 at DNA breaks involves its binding to phosphorylated histone H2AX. J Biol Chem 278:19579–19582

    Article  CAS  Google Scholar 

  • Watson JD, Crick FH (1953) Genetical implications of the structure of deoxyribonucleic acid. Nature 171:964–967

    Article  CAS  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

    Article  CAS  Google Scholar 

  • Wong EA, Capecchi MR (1987) Homologous recombination between coinjected DNA sequences peaks in early to mid-S phase. Mol Cell Biol 7:2294–2295

    CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Xu N, Hegarat N, Black EJ, Scott MT, Hochegger H, Gillespie DA (2010) Akt/PKB suppresses DNA damage processing and checkpoint activation in late G2. J Cell Biol 190:297–305

    Article  CAS  Google Scholar 

  • Yang H, Wen YY, Zhao R, Lin YL, Fournier K, Yang HY, Qiu Y, Diaz J, Laronga C, Lee MH (2006) DNA damage-induced protein 14-3-3 sigma inhibits protein kinase B/Akt activation and suppresses Akt-activated cancer. Cancer Res 66:3096–3105

    Article  CAS  Google Scholar 

  • Yuan ZM, Huang Y, 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

    Article  CAS  Google Scholar 

  • Zhang Z, Fan HY, Goldman JA, Kingston RE (2007) Homology-driven chromatin remodeling by human RAD54. Nat Struct Mol Biol 14:397–405

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Université Paris Sud, Laboratoire «Stabilité Génétique et Oncogenèse» CNRS, UMR 8200 GR – PR2, 114 Rue Edouard Vaillant, 94805, Villejuif, France

    Aurélia Barascu & Bernard S. Lopez

  2. Institut de radiobiologie cellulaire et moléculaire, Institut de Cancérologie Gustave-Roussy CNRS, UMR217, Villejuif, France

    Aurélia Barascu & Bernard S. Lopez

  3. Laboratoire “Biologie cellulaire de l’intégrité du génome”, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France

    Anastazja Grabarz

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  1. Aurélia Barascu
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  2. Anastazja Grabarz
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  3. Bernard S. Lopez
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Correspondence to Bernard S. Lopez .

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    Sylvaine Renault

  2. Cellectis SA, Rue de la Croix Jarry 8, Paris, 75013, France

    Philippe Duchateau

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Barascu, A., Grabarz, A., Lopez, B.S. (2013). Homologous Recombination in Mammals. In: Renault, S., Duchateau, P. (eds) Site-directed insertion of transgenes. Topics in Current Genetics, vol 23. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4531-5_4

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