Abstract
A paradigm shift has occurred over the last few years in the understanding of homologous recombination. It has long been known that DNA double-strand breaks (DSBs) in yeast are potent inducers of homologous recombination and that homologous recombination is the major pathway in yeast to repair DSBs (Chapter 16, Vol. 1). Compared with nonhomologous repair, homologous recombination has generally been considered to be inconsequential as a DSB repair pathway in mammalian cells. However, homologous repair can precisely restore the damaged DNA to its original sequence, suggesting that it should be a preferred pathway for repair, at least under some circumstances. Recently, direct examination of repair products in mammalian cells has demonstrated the importance of homologous recombination during the repair of DSBs. Supporting this conclusion has been the identification of DNA repair defects in mutant cell lines and the construction of mouse knockouts of genes implicated in homologous recombination. This chapter discusses basic parameters of DSB repair by homologous recombination in mammalian cells and emerging evidence for the involvement of various proteins in the repair process.
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References
Akgün, E., J. Zahn, S. Baumes, G. Brown, F. Liang, P. J. Romanienko et al. 1997. Palindrome resolution and recombination in the mammalian germ line. Mol. Cell. Biol. 17 (9): 5559–5570.
Ashley, C. T., and S. T. Warren. 1995. Trinucleotide repeat expansion and human disease. Ann. Rev. Genet. 29: 703–728.
Baker, M. D., and L. R. Read. 1992. Ectopic recombination within homologous immunoglobulin mu gene constant regions in a mouse hybridoma cell line. Mol. Cell. Biol. 12 (10): 4422–4432.
Baker, M. D., and L. R. Read. 1995. High-frequency gene conversion between repeated C mu sequences integrated at the chromosomal immunoglobulin mu locus in mouse hybridoma cells. Mol. Cell. Biol. 15 (2): 766–771.
Baumann, P., F. E. Benson, and S. C. West. 1996. Human Rad51 protein promotes ATP-dependent homolgous pairing and strand transfer reactions in vitro. Cell 87: 757–766.
Belfort, M. 1997. Homing endonucleases: keeping the house in order. Nucleic Acids Res. 25: 3379–3388.
Belmaaza, A., E. Milot, J. F. Villemure, and P. Chartrand. 1994. Interference of DNA sequence divergence with precise recombinational DNA repair in mammalian cells. EMBO.1. 13 (22): 5355–5360.
Benjamin, M. B., and J. B. Little. 1992. X rays induce interallelic homologous recombination at the human thymidine kinase gene. Mol. Cell. Biol. 12 (6): 2730–2738.
Benjamin, M. B., H. Potter, D. W. Yandell, and J. B. Little. 1991. A system for assaying homologous recombination at the endogenous human thymidine kinase gene. Proc. Natl. Acad. Sci. USA 88 (15): 6652–6656.
Boland, C. R. 1998. Hereditary nonpolyposis colorectal cancer, in The Genetic Basis of Human Cancer ( Vogelstein, B. and K. W. Kinzler, eds.), McGraw-Hill, New York, NY, pp. 333–346.
Bollag, R. J., and R. M. Liskay. 1991. Direct-repeat analysis of chromatid interactions during intrachromosomal recombination in mouse cells. Mol. Cell. Biol. 11 (10): 4839–4845.
Bootsma, D., K. H. Kraemer, J. E. Cleaver, and J. H. J. Hoeijmakers. 1998. Nucleotide excision repair systems: xeroderma pigmentosa, Cockayne syndrome, and trichothiodystrophy, in The Genetic Basis of Human Cancer ( Vogelstein, B. and K. W. Kinzler, eds.), McGraw-Hill, New York, NY, pp. 245–274.
Brenneman, M., E. S. Gimble, and J. H. Wilson. 1996. Stimulation of intrachromosomal homologous recombination in human cells by electroporation with site-specific endonucleases. Proc. Natl. Acad. Sci. USA 93 (8): 3608–3612.
Brenneman, M. A., A. E. Weiss, J. A. Nickoloff, and D. J. Chen. 2000. XRCC3 is required for efficient repair of chromosome breaks by homologous recombination. Mutat. Res. 459: 89–97.
Bryant, F. E. 1989. Restriction enonuclease-and radiation-induced DNA double-strand breaks and chromosomal aberrations: similarities and differences, in Chromosomal Aberrations: Basic and Applied Aspects ( Obe G. and A. T. Natarajan, eds.), Springer, Berlin, pp. 61–69.
Capecchi, M. R. 1989. Altering the genome by homologous recombination. Science 244: 1288–1292.
Carney, J. P., R. S. Maser, H. Olivares, E. M. Davis, M. Le Beau, J. R. Yates, 3rd, et al. 1998. The hMre1l/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell 93 (3): 477–486.
Cartwright, R., A. M. Dunn, P. J. Simpson, C. E. Tambini, and J. Thacker. 1998. Isolation of novel human and mouse genes of the recA/RAD51 recombination-repair gene family. Nucleic Acids Res. 26 (7): 1653–1659.
Cartwright, R., C. E. Tambini, P. J. Simpson, and J. Thacker. 1998. The XRCC2 DNA repair gene from human and mouse encodes a novel member of the recA/RAD51 family. Nucleic Acids Res. 26 (13): 3084–3089.
Cavenee, W. K., T. P. Dryja, R. A. Phillips, W. F. Benedict, R. Godbout, B. L. Gallie, et al. 1983. Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. Nature 305: 779–784.
Chen, J., D. P. Silver, D. Walpita, S. B. Cantor, A. F. Gazdar, G. Tomlinson, F. J. Couch, B. L. Weber, T. Ashley, D. M. Livingston, and R. Scully. 1998. Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells. Mol. Cell 2 (3): 317–328.
Chen, P. L., C. F. Chen, Y. Chen, J. Xiao, Z. D. Sharp, and W. H. Lee. 1998. The BRC repeats in BRCA2 are critical for RAD51 binding and resistance to methyl methanesulfonate treatment. Proc. Natl. Acad. Sci. USA 95 (9): 5287–5292.
Choulika, A., A. Perrin, B. Dujon, and J.-F. Nicolas. 1995. Induction of homologous recombination in mammalian chromosomes by using the I-SceI system of Saccharomyces cerevisiae. Mol. Cell. Biol. 15: 1963–1973.
Clikeman, J. A., G. J. Khalsa, S. L. Barton, and J. A. Nickoloff. 2001. Homologous recombinational repair of double-strand breaks in yeast is enhanced by MAT heterozygosity through yKudependent and independent mechanisms. Genetics (in press).
Cohen-Tannoudji, M., S. Robine, A. Choulika, D. Pinto, F. El Marjou, C. Babinet, D. Louvard, and F. Jaisser. 1998. I-SceI-induced gene replacement at a natural locus in embryonic stem cells. Mol. Cell. Biol. 18 (3): 1444–1448.
Colleaux, L., L. d’Auriol, M. Betermier, G. Cottarel, A. Jacquier, F. Galibert, and B. Dujon. 1986. Universal code equivalent of a yeast mitochondrial intron reading frame is expressed into E. coli as a specific double strand endonuclease. Cell 44: 521–533.
Colleaux, L., L. d’Auriol, F. Gailbert, and B. Dujon. 1988. Recognition and cleavage site of the intron-encoded omega transposase. Proc. Natl. Acad. Sci. USA 85: 6022–6026.
Collick, A., J. Drew, J. Penberth, P. Bois, J. Luckett, F. Scaerou, A. Jeffreys, and W. Reik. 1996. Instability of long inverted repeats within mouse transgenes. EMBO J. 15: 1163–1171.
Connor, F., D. Bertwistle, P. J. Mee, G. M. Ross, S. Swift, E. Grigorieva, et al. 1997. Tumorigenesis and a DNA repair defect in mice with a truncating Brca2 mutation. Nature Genet. 17 (4): 423–430.
Cooper, D. N., M. Krawczak, and S. E. Antonarakis. 1998. The nature of human gene mutation, in The Genetic Basis of Human Cancer ( Vogelstein, B. and K. W. Kinzler, eds.), McGraw-Hill, New York, pp. 64–92.
Coquelle, A., E. Pipiras, F. Toledo, G. Buttin, and M. Debatisse. 1997. Expression of fragile sites triggers intrachromosomal mammalian gene amplification and sets boundaries to early amplicons. Cell 89 (2): 215–225.
de Wind, N., M. Dekker, A. Berns, M. Radman, and H. te Riele. 1995. Inactivation of the mouse Msh2 gene results in mismatch repair deficiency, methylation tolerance, hyperrecombination, and predisposition to cancer. Cell 82: 321–330.
Dolganov, G. M., R. S. Maser, A. Novikov, L. Tosto, S. Chong, D. A. Bressan, and J. H. J. Petrini. 1996. Human Rad50 is physically associated with human Mrel l: identification of a conserved multiprotein complex implicated in recombinational DNA repair. Mol. Cell. Biol. 16: 4832–4841.
Donoho, G., M. Jasin, and P. Berg. 1998. Analysis of gene targeting and intrachromosomal homologous recombination stimulated by genomic double-strand breaks in mouse embryonic stem cells. Mol. Cell. Biol. 18: 4070–4078.
Dosanjh, M. K., D. W. Collins, W. Fan, G. G. Lennon, J. S. Albala, Z. Shen, and D. Schild. 1998. Isolation and characterization of RAD5 1 C, a new human member of the RAD51 family of related genes. Nucleic Acids Res. 26 (5): 1179–1184.
Dronkert, M. L. G, H. B. Beverloo, R. D. Johnson, J. H. J. Hoeijmakers, M. Jasin, and R. Kanaar. 2000. Mouse RAD54 affects DNA double-strand break repair and sister chromatid exchange. Mol. Cell. Biol. 20: 3147–3156.
Dujon, B. 1989. Group I introns as mobile genetic elements: facts and mechanistic speculations: a review. Gene 82: 91–114.
Elliott, B., C. Richardson, J. Winderbaum, J. A. Nickoloff, and M. Jasin. 1998. Gene conversion tracts from double-strand break repair in mammalian cells. Mol. Cell. Biol. 18: 93–101.
Engels, W. R., D. M. Johnson-Schlitz, W. B. Eggleston, and J. Sved. 1990. High-frequency P element loss in Drosophila is homolog dependent. Cell 62 (3): 515–525.
Essers, J., R. W. Hendriks, S. M. A. Swagemakers, C. Troelstra, J. de Wit, D. Bootsma, et al. 1997. Disruption of mouse RAD54 reduces ionizing radiation resistance and homologous recombination. Cell 89: 195–204.
Fairhead, C., and B. Dujon. 1993. Consequences of unique double-stranded breaks in yeast chromosomes: death or homozygosis. Mol. Gen. Genet. 240: 170–178.
Ferguson, D. O., and W. K. Holloman. 1996. Recombinational repair of gaps in DNA is asymmetric in Ustilago maydis and can be explained by a migrating D-loop model. Proc. Natl. Acad. Sci. USA 93: 5419–5424.
Ferguson, M., and D. C. Ward. 1992. Cell cycle dependent chromosomal movement in pre-mitotic human T-lymphocyte nuclei. Chromosoma 101 (9): 557–565.
Formosa, T., and B. M. Alberts. 1986. DNA synthesis dependent on genetic recombination: characterization of a reaction catalyzed by purified bacteriophage T4 proteins. Cell 47 (5): 793–806.
Frank, K. M., J. M. Sekiguchi, K. J. Seidl, W. Swat, G. A. Rathbun, H. L. Cheng, et al. 1998. Late embryonic lethality and impaired V(D)J recombination in mice lacking DNA ligase IV. Nature 396 (6707): 173–177.
Fukushige, S., and B. Sauer. 1992. Genomic targeting with a positive-selection lox integration vector allows highly reproducible gene expression in mammalian cells. Proc. Natl. Acad. Sci. USA 89: 7905–7909.
Fuller, L. F., and R. B. Painter. 1988. A Chinese hamster ovary cell line hypersensitive to ionizing radiation and deficient in repair replication. Mutat. Res. 193: 109–121.
Gao, Y., J. Chaudhuri, C. Zhu, L. Davidson, D. T. Weaver, and F. W. Alt. 1998. A targeted DNAPKcs-null mutation reveals DNA-PK-independent functions for KU in V(D)J recombination. Immunity 9 (3): 367–376.
Gao, Y., Y. Sun, K. M. Frank, P. Dikkes, Y. Fujiwara, K. J. Seidl, et al. 1998. A critical role for DNA end-joining proteins in both lymphogenesis and neurogenesis. Cell 95 (7): 891–902.
Giaccia, A., R. Weinstein, J. Hu, and T. D. Stamato. 1985. Cell cycle-dependent repair of double-strand DNA breaks in a gamma-ray-sensitive Chinese hamster cell. Somat. Cell Mol. Genet 11 (5): 485–491.
Gimble, F. S., and J. Thorner. 1992. Homing of a DNA endonuclease gene by meiotic gene conversion in Saccharomyces cerevisiae. Nature 357: 301–306.
Gloor, G. B., and D. H. Lankenau. 1998. Gene conversion in mitotically dividing cells: a view from Drosophila. Trends Genet 14 (2): 43–46.
Gordenin, D. A., and M. A. Resnick. 1998. Yeast ARMs (DNA at-risk motifs) can reveal sources of genome instability. Mutat Res 400 (1–2): 45–58.
Gowen, L. C., A. V. Avrutskaya, A. M. Latour, B. H. Koller, and S. A. Leadon. 1998. BRCA1 required for transcription-coupled repair of oxidative DNA damage. Science 281: 1009–1012.
Gowen, L. C., B. L. Johnson, A. M. Latour, K. K. Sulik, and B. H. Koller. 1996. Brcal deficiency results in early embryonic lethality characterized by neuroepithelial abnormalities. Nature Genet 12: 191–194.
Griffin, C. S., P. J. Simpson, C. R. Wilson, and J. Thacker. 2000. Mammalian recombination-repair genes XRCC2 and XRCC3 promote correct chromosome segregation. Nat. Cell. Biol. 2: 757–761.
Griffith, J. D., L. Comeau, S. Rosenfield, R. M. Stansel, A. Bianchi, H. Moss, and T. de Lange. 1999. Mammalian telomeres end in a large duplex loop. Cell 97: 503–514.
Gu, Y., K. J. Seidl, G. A. Rathbun, C. Zhu, J. P. Manis, N. van der Stoep, et al. 1997. Growth retardation and leaky SCID phenotype of Ku70-deficient mice. Immunity 7: 653–665.
Haber, J. E. 1998. The many interfaces of Mrell. Cell 95 (5): 583–586.
Hakem, R., J. L. de la Pompa, C. Sirard, R. Mo, M. Woo, A. Hakem, et al. 1996. The tumor suppressor gene Brcal is required for embryonic cellular proliferation in the mouse. Cell 85: 1009–1023.
Hasty, P., J. Rivera-Perez, and A. Bradley. 1992. The role and fate of DNA ends for homologous recombination in embryonic stem cells. Mol. Cell. Biol. 12 (6): 2464–2474.
Hays, S. L., A. A. Firmenich, and R. Berg. 1995. Complex formation in yeast double-strand break repair: Participation of Rad51, Rad52, Rad55, and Rad57 proteins. Proc. Natl. Acad. Sci. 92: 6925–6929.
Holmes, A. M., and J. E. Haber. 1999. Double-strand break repair in yeast requires both leading and lagging strand DNA polymerases. Cell 96 (3): 415–424.
Hsieh, C. L., C. F. Arlett, and M. R. Lieber. 1993. V(D)J recombination in ataxia telangiectasia, Bloom’s syndrome, and a DNA ligase I-associated immunodeficiency disorder. J. Biol. Chem. 268(27): 20,105–20, 109.
Ivics, Z., P. B. Hackett, R. H. Plasterk, and Z. Izsvak. 1997. Molecular reconstruction of Sleeping Beauty, a Tcl-like transposon from fish, and its transposition in human cells. Cell 91 (4): 501–510.
Jasin, M. 2000. Chromosome breaks and genomic instability. Cancer Invest. 18: 78–76.
Jasin, M. 1996. Genetic manipulation of genomes with rare-cutting endonucleases. Trends Genet. 12: 224–228.
Jasin, M. 1999. LOH and mitotic recombination, In DNA Alterations in Cancer: Genetic and Epigenetic Changes. ( Ehrlich, M. eds.), Eaton Publishing, Natick, MA.
Jasin, M., and P. Berg. 1988. Homologous integration in mammalian cells without target gene selection. Genes Dev. 2: 1353–1363.
Jasin, M., J. deVilliers, F. Weber, and W. Schaffner. 1985. High frequency of homologous recombination in mammalian cells between endogenous and introduced SV40 genomes. Cell 43: 695–703.
Jasin, M., and F. Liang. 1991. Mouse embryonic stem cells exhibits high levels of extrachromosomal homologous recombination in a chloramphenicol acetyltransferase assay system. Nucleic Acids Res. 19: 7171–7175.
Johnson, R. D., and L. S. Symington. 1995. Functional differences and interactions among the putative RecA homologs Rad51, Rad55, and Rad57. Mol. Cell. Biol. 15: 4843–4850.
Johnson, R. D., and M. Jasin. 2000. Sister-chromatid gene conversion is a prominent DNA repair pathway in mammalian cells, EMBO J. 19: 3398–3407.
Johnson, R. D., N. Liu, and M. Jasin. 1999. Mammalian XRCC2 promotes the repair of DNA double-strand breaks by homologous recombination. Nature 401: 397–399.
Jones, N. J., R. Cox, and J. Thacker. 1987. Isolation and cross-sensitivity of X-ray-sensitive mutants of V79–4 hamster cells. Mut. Res. 183: 279–286.
Kadyk, L. C., and L. H. Hartwell. 1992. Sister chromatids are preferred over homologs as substrates for recombinational repair in Saccharomyces cerevisiae. Genetics 132: 387–402.
Kass, D. H., M. A. Batzer, and R. L. Deininger. 1995. Gene conversion as a secondary mechanism of short interspersed element (SINE) evolution. Mol. Cell. Biol. 15 (1): 19–25.
Kazazian, H. H., Jr., and J. V. Moran. 1998. The impact of L1 retrotransposons on the human genome. Nature Genet 19 (1): 19–24.
Kinzler, K. W., and B. Vogelstein. 1998. Familial cancer syndromes: the role of caretakers and gatekeepers, in ( Vogelstein, B. and K. W. Kinzler, eds.), The Genetic Basis of Human Cancer McGraw-Hill, New York, NY, pp. 241–242.
LaSalle, J. M., and M. Lalande. 1996. Homologous association of oppositely imprinted chromosomal domains. Science 272 (5262): 725–728.
Leach, D. R. F. 1994. Long DNA palindromes, cruciform structures, genetic instability and secondary structure repair. BioEssays 16: 893–900.
Lewis, S. 1994. P nucleotide insertions and the resolution of hairpin DNA structures in mammalian cells. Proc. Natl. Acad. Sci. USA 91: 1332–1336.
Lewis, S. M. 1994. The mechanism of V(D)J joining: lessons from molecular, immunological and comparative analyses. Adv. Immunol. 56: 27–149.
Li, G. C., H. Ouyang, X. Li, H. Nagasawa, J. B. Litle, D. J. Chen, et al. 1998. Ku70: a candidate tumor suppressor gene for murine T cell lymphoma. Mol. Cell 2: 1–8.
Liang, E, M. Han, R. J. Romanienko, and M. Jasin. 1998. Homology-directed repair is a major double-strand break repair pathway in mammalian cells. Proc. Natl. Acad. Sci. USA 95: 5172–5177.
Liang, F., and M. Jasin. 1996. Ku80 deficient cells exhibit excess degradation of extrachromosomal DNA. J. Biol. Chem. 271: 14,405–14, 411.
Liang, F., R. J. Romanienko, D. T. Weaver, R. A. Jeggo, and M. Jasin. 1996. Chromosomal double-strand break repair in Ku80 deficient cells. Proc. Natl. Acad. Sci. USA 93: 8929–8933.
Lim, D. -S., and P. Hasty. 1996. A mutation in mouse rad51 results in an early embryonic lethal that is suppressed by a mutation in p53. Mol. Cell. Biol. 16: 7133–7143.
Lin, F. -L., K. Sperle, and N. Sternberg. 1984. Model for homologous recombination during transfer of DNA into mouse L cells: Role for DNA ends in the recombination process. Mol. Cell. Biol. 4: 1020–1034.
Lin, Y., T. Lukacsovich, and A. S. Waldman. 1999. Multiple pathways of repair of DNA double-strand breaks in mammalian chromosomes. Mol. Cell. Biol., 19: 8353–8360.
Liskay, R. M., and J. L. Stachelek. 1983. Evidence for intrachromosomal gene conversion in cultured mouse cells. Cell 35 (1): 157–165.
Liu, C. Y., A. Fleskin-Nikitin, S. Li, Y. Zeng, and W. H. Lee. 1996. Inactivation of the mouse BRCA1 gene leads to failure in the morphogenesis of the egg cylinder in early postimplantation development. Genes Dey. 10: 1835–1843.
Liu, N., J. E. Lamerdin, R. S. Tebbs, D. Schild, J. D. Tucker, M. R. Shen, et al. 1998. XRCC2 and XRCC3, new human Rad51-family members, promote chromosome stability and protect against DNA cross-links and other damages. Mol. Cell 1: 783–793.
Loeb, L. A. 1991. Mutator phenotype may be required for multistage carcinogenesis. Cancer Res 51 (12): 3075–3079.
Lukacsovich, T., D. Yang, and A. S. Waldman. 1994. Repair of a specific double-strand break generated within a mammalian chromosome by yeast endonuclease I-SceI. Nucleic Acids Res. 22: 5649–5657.
Ma, C., S. Martin, B. Trask, and J. L. Hamlin. 1993. Sister chromatid fusion initiates amplification of the dihydrofolate reductase gene in Chinese hamster cells. Genes. Dey. 7 (4): 605–620.
Marmorstein, L. Y., T. Ouchi, and S. A. Aaronson. 1998. The BRCA2 gene product functionally interacts with p53 and RAD51. Proc. Natl. Acad. Sci. USA 95(23): 13,869–13, 874.
McClintock, B. 1941. The stability of broken ends of chromosomes in Zea mays. Genetics 41: 234–282.
Meyn, M. S. 1993. High spontaneous intrachromosomal recombination rates in ataxia-telangiectasia. Science 260 (5112): 1327–1330.
Miyazaki, W. Y., and T. L. Orr-Weaver. 1994. Sister-chromatid cohesion in mitosis and meiosis. Ann. Rev. Genet. 28: 167–187.
Mizuta, R., J. M. LaSalle, H. L. Cheng, A. Shinohara, H. Ogawa, N. Copeland, et al. 1997. RAB22 and RAB 163/mouse BRCA2: proteins that specifically interact with the RAD51 protein. Proc. Natl. Acad. Sci. USA 94 (13): 6927–6932.
Monteilhet, C., A. Perrin, A. Thierry, L. Colleaux, and B. Dujon. 1990. Purification and characterization of the in vitro activity of I-SceI, a novel and highly specific endonuclease encoded by a group I intron. Nucleic Acids Res. 18: 1407–1413.
Moolgavkar, S. H., and A. G. Knudson, Jr. 1981. Mutation and cancer: a model for human carcinogenesis. J. Natl. Cancer Inst. 66 (6): 1037–1052.
Morimatsu, M., G. Donoho, and P. Hasty. 1998. Cells deleted for Brca2 COOH terminus exhibit hypersensitivity to gamma-radiation and premature senescence. Cancer Res. 58 (15): 3441–3447.
Morita, T., Y. Yoshimura, A. Yamamoto, K. Kurata, M. Mori, H. Yamamoto, and A. Matsushiro. 1993. A mouse homolog of the Escherichia coli recA and Saccharomyces cerevisiae RAD51 genes. Proc. Natl. Acad. Sci. USA 90: 6577–6580.
Moynahan, M. E., and M. Jasin. 1997. Loss of heterozygosity induced by a chromosomal double-strand break. Proc. Natl. Acad. Sci. USA 94: 8988–8993.
Moynahan, M. E., J. W. Chiu, B. H. Koller, and M. Jasin. 1999. Brcal controls homology-directed DNA repair. Molecular Cell 4: 511–518.
Nickoloff, J. A. 1992. Transcription enhances intrachromosomal homologous recombination in mammalian cells. Mol. Cell. Biol. 12 (12): 5311–5318.
Nussenzweig, A., C. Chen, V. da Costa Soares, M. Sanchez, K. Sokol. et al. 1996. Requirement for Ku80 in growth and immunoglobulin V(D)J recombination. Nature 382: 551–555.
Park, M. S. 1995. Expression of human RAD52 confers resistance to ionizing radiation in mammalian cells. J. Biol. Chem. 270(26): 15,467–15, 470.
Patel, K. J., V. P. Vu, H. Lee, A. Corcoran, F. C. Thistlethwaite, M. J. Evans, et al. 1998. Involvement of Brca2 in DNA repair. Mol. Cell. 1 (3): 347–357.
Paull, T. T., and M. Gellert. 1998. The 3’ to 5’ exonuclease activity of Mre 11 facilitates repair of DNA double-strand breaks. Mol. Cell 1 (7): 969–979.
Perrin, A., M. Buckle, and B. Dujon. 1993. Asymmetrical recognition and activity of the 1-SceI endonuclease on its site an on intron-exon junctions. EMBO J. 12: 2939–2947.
Petes, T. D., R. E. Malone, and L. S. Symington. 1991. Recombination in yeast, in The Molecular and Cellular Biology of the Yeast Saccharomyces: genome Dynamics, Protein Synthesis, and Energetics. (Broach, J. R., J. R. Pringle, and E. W. Jones, eds.), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 407–521.
Petrini, J. H. J., M. E. Walsh, C. DiMare, J. R. Korenberg, X. -N. Chen, and D. T. Weaver. 1995. Isolation and characterization of the human MRE1 1 homologue. Genomics 29: 80–86.
Phillips, J. W., and W. F. Morgan. 1994. Illegitimate recombination induced by DNA double-strand breaks in a mammalian chromosome. Mol. Cell. Biol. 14: 5794–5803.
a.Pierce, A. J., R. D. Johnson, L. H. Thompson, and M. Jasin. 1999. The Rad51-related protein XRCC3 promotes homology-directed repair of damage in mammalian cells. Genes Del,. 13: 2633–2638.
Pipiras, E., A. Coquelle, A. Bieth, and M. Debatisse. 1998. Interstitial deletions and intrachromosomal amplification initiated from A double-strand break targeted to a mammalian chromosome. EMBO J. 17 (1): 325–333.
Pittman, D. L., L. R. Weinberg, and J. C. Schimenti. 1998. Identification, characterization, and genetic mapping of Rad51d, a new mouse and human RAD51/RecA-related gene. Genomics 49 (1): 103–111.
a.Pittman, D. L., and J. C. Schimenti. 2000. Midgestation lethality in mice deficient for the RecArelated gene, Rad51d/Rad5113. Genesis 26: 167–173.
Plasterk, R. H. 1991. The origin of footprints of the Tcl transposon of Caenorhabditis elegans. EMBO J. 10 (7): 1919–1925.
Plessis, A., A. Perrin, J. E. Haber, and B. Dujon. 1992. Site-specific recombination determined by I-SceI, a mitochondrial group I intron-encoded endonuclease expressed in the yeast nucleus. Genetics 130: 451–460.
Rayssiguier, C., D. S. Thaler, and M. Radman. 1989. The barrier to recombination between Esche ri chia coli and Salmonella typhimurium is disrupted in mismatch-repair mutants. Nature 342: 396–401.
Reiter, L. T., T. Murakami, T. Koeuth, L. Pentao, D. M. Muzny, R. A. Gibbs, and J. R. Lupski. 1996. A recombination hotspot responsible for two inherited peripheral neuropathies is located near a mariner transposon-like element. Nature. Genet. 12 (3): 288–297.
Rice, M. C., S. T. Smith, F. Bullrich, P. Havre, and E. B. Kmiec. 1997. Isolation of human and mouse genes based on homology to REC2, a recombinational repair gene from the fungus Usti-lago maydis. Proc. Natl. Acad. Sci. USA 94 (14): 7417–7422.
Richard, M., A. Belmaaza, N. Gusew, J. C. Wallenburg, and P. Chartrand. 1994. Integration of a vector containing a repetitive LINE-1 element in the human genome. Mol. Cell. Biol. 14 (10): 6689–6695.
Richardson, C., B. Elliott, and M. Jasin. 1999. Chromosomal double-strand breaks introduced in mammalian cells by expression of I-SceI endonuclease, in DNA Repair Protocols: Eukaryotic Systems ( Henderson, D. S. ed.), Humana Press, Totowa, NJ, pp. 453–464.
Richardson, C., and M. Jasin. 2000. Frequent chromosomal translocations induced by DNA double-strand breaks, Nature 405: 697–700.
Richardson, C., and M. Jasin. 2000. Coupled homologous and nonhomologous repair of a double-strand break preserves genomic integrity in mammalian cells. Mol. Cell. Biol. 20: in press.
Richardson, C., M. E. Moynahan, and M. Jasin. 1998. Double-strand break repair by inter-chromosomal recombination: suppression of chromosomal translocations. Genes Dev. 12: 3831–3842.
Rijkers, T., J. Van Den Ouweland, B. Morolli, A. G. Rolink, W. M. Baarends, P. P. Van Sloun. et al. 1998. Targeted inactivation of mouse RAD52 reduces homologous recombination but not resistance to ionizing radiation. Mol. Cell. Biol. 18 (11): 6423–6429.
Roth, D. B., and J. H. Wilson. 1985. Mechanisms of nonhomologous recombination in mammalian cells. Mol. Cell. Biol. 5: 2599–2607.
Rouet, P., F. Smih, and M. Jasin. 1994. Expression of a site-specific endonuclease stimulates homologous recombination in mammalian cells. Proc. Natl. Acad. Sci. USA 91: 6064–6068.
Rouet, P., F. Smih, and M. Jasin. 1994. Introduction of double-strand breaks into the genome of mouse cells by expression of a rare-cutting endonuclease. Mol. Cell. Biol. 14: 8096–8106.
Sargent, R. G., M. A. Brenneman, and J. H. Wilson. 1997. Repair of site-specific double-strand breaks in a mammalian chromosome by homologous and illegitimate recombination. Mol. Cell. Biol. 17 (1): 267–277.
Scheerer, J. B., and G. M. Adair. 1994. Homology dependence of targeted recombination at the Chinese hamster APRT locus. Mol. Cell. Biol. 14 (10): 6663–6673.
Schmid, C. W. 1996. Alu: structure, origin, evolution, significance and function of one-tenth of human DNA. Prog. Nucleic Acid Res. Mol. Biol. 53: 283–319.
Scully, R., J. Chen, A. Plug, Y. Xiao, D. Weaver, J. Feunteun, T. Ashley, and D. M. Livingston. 1997. Association of BRCA1 with Rad51 in mitotic and meiotic cells. Cell 88 (2): 265–275.
Sharan, S. K., M. Morimatsu, U. Albrecht, D. -S. Lim, E. Regel, C. Dinh, A. Sands, G. Eichele, P. Hasty, and A. Bradley. 1997. Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2. Nature 386: 804–810.
Shen, S. X., Z. Weaver, X. Xu, C. Li, M. Weinstein, L. Chen, X. Y. Guan, T. Ried, and C. X. Deng. 1998. A targeted disruption of the murine Brcal gene causes gamma-irradiation hypersensitivity and genetic instability. Oncogene 17 (24): 3115–3124.
a.Schild, D., Y. Lio, D. W. Collins, T. Tsomondo, T., and D. J. Chen. 2000. Evidence for simultaneous protein interactions between human Rad51 paralogs. J. Biol. Chem. 275: 16443–16449.
Shinohara, A., H. Ogawa, and T. Ogawa. 1992. Rad51 protein involved in repair and recombination in S. cerevisiae is a recA-like protein. Cell 69: 457–470.
Shu Z., S. Smith, L. Wang, M. C. Rice, and E. B. Kmiec. 1999. Disruption of muREC2/ RAD51L1 in mice results in early embryonic lethality which can Be partially rescued in a p.53 (I) background. Mol. Cell. Biol. 19: 8686–8693.
Shulman, M. J., C. Collins, A. Connor, L. R. Read, and M. D. Baker. 1995. Interchromosomal recombination is suppressed in mammalian somatic cells. EMBO J. 14 (16): 4102–4107.
Smih, F., P. Rouet, P. J. Romanienko, and M. Jasin. 1995. Double-strand breaks at the target locus stimulate gene targeting in embryonic stem cells. Nucleic Acids Res. 23: 5012–5019.
Smith, A. J., and P. Berg. 1984. Homologous recombination between defective neo genes in mouse 3T6 cells. Cold Spring Harb. Symp. Quant. Biol. 49: 171–181.
Sprung, C. M., G. E. Reynolds, M. Jasin, and J. P. Murnane. 1999. Chromosome healing in mouse embryonic stem cells. Proc. Natl. Acad. Sci. USA 96: 6781–6786.
Subramani, S., and B. L. Seaton. 1988. Homologous recombination in mitotically dividing mammalian cells, in Genetic Recombination, ( Kucherlapati, R. and G. R. Smith, eds.), American Society for Microbiology, Washington, DC, pp. 549–573.
Sung, P. 1997. Yeast Rad55 and Rad57 proteins form a heterodimer that functions with replication protein A to promote DNA strand exchange by Rad51 recombinase. Genes Dey 11 (9): 1111–1121.
Suzuki, A., J. L. de la Pompa, R. Hakem, A. Elia, R. Yoshida, R. Mo, et al. 1997. Brca2 is required for embryonic cellular proliferation in the mouse. Genes Dey 11 (10): 1242–1252.
Szostak, J. W., T. L. Orr-Weaver, R. J. Rothstein, and F. W. Stahl. 1983. The double-strandbreak repair model for recombination. Cell 33: 25–35.
Taccioli, G. E., A. G. Amatucci, H. J. Beamish, D. Gell, X. H. Xiang, M. I. Torres Arzayus, et al. 1998. Targeted disruption of the catalytic subunit of the DNA-PK gene in mice confers severe combined immunodeficiency and radiosensitivity. Immunity 9 (3): 355–366.
Taccioli, G. E., G. Rathbun, E. Oltz, T. Stamato, P. A. Jeggo, and F. W. Alt. 1993. Impairment of V(D)J recombination in double-strand break repair mutants. Science 260: 207–210.
Taghian, D. G., and J. A. Nickoloff. 1997. Chromosomal double-strand breaks induce gene conversion at high frequency in mammalian cells. Mol. Cell. Biol. 17: 6386–6393.
to Riele, H., E. R. Maandag, and A. Berns. 1992. Highly efficient gene targeting in embryonic stem cells through homologous recombination with isogenic DNA constructs. Proc. Natl. Acad. Sci. USA 89: 5128–5132.
Terasima, T., and L. J. Tolmach. 1961. Variations in several responses of HeLa cells to X-irradiation during the division cycle. J. Biophys. 3: 11–33.
Tremblay, A., M. Jasin, and P. Chartrand. 2000. A double-strand break in a chromosomal LINE element can be repaired by gene conversion with various endogenous LINE elements in mouse cells. Mol. Cell. Biol. 20: 54–60.
Thierry, A., A. Perrin, J. Boyer, C. Fairhead, B. Dujon, B. Frey, and G. Schmitz. 1991. Cleavage of yeast and bacteriophage T7 genomes at a single site using the rare cutter endonuclease I-SceI. Nucleic Acids Res. 19: 189–190.
Tsuzuki, T., Y. Fujii, K. Sakumi, Y. Tominaga, K. Nakao, M. Sekiguchi, A. Matsushiro, Y. Yoshimura, and T. Monta. 1996. Targeted disruption of the Rad51 gene leads to lethality in embryonic mice. Proc. Natl. Acad. Sci. USA 93: 6236–6340.
van Steensel, B., A. Smogorzewska, and T. de Lange. 1998. TRF2 protects human telomeres from end-to-end fusions. Cell 92 (3): 401–413.
Varon, R., C. Vissinga, M. Platzer, K. M. Cerosaletti, K. H. Chrzanowska, K. Saar, et al. 1998. Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell 93 (3): 467–476.
Vispe, S., C. Cazaux, C. Lesca, and M. Defais. 1998. Overexpression of Rad51 protein stimulates homologous recombination and increases resistance of mammalian cells to ionizing radiation. Nucleic Acids Res. 26 (12): 2859–2864.
Vogelstein, B., and K. W. Kinzler (eds.). 1998. The Genetic Basis of Human Cancer. McGraw-Hill, New York.
Waldman, A. S., and R. M. Liskay. 1988. Dependence of intrachromosomal recombination in mammalian cells on uninterrupted homology. Mol. Cell. Biol. 8: 5350–5357.
Waldman, A. S., and R. M. Liskay. 1987. Differential effects of base-pair mismatch on intra-chromosomal versus extrachromosomal recombination in mouse cells. Proc. Natl. Acad. Sci. USA 84 (15): 5340–5344.
Wang, P., R. H. Zhou, Y. Zou, C. K. Jackson-Cook, and L. R Povirk. 1997. Highly conservative reciprocal translocations formed by apparent joining of exchanged DNA double-strand break ends. Proc. Natl. Acad. Sci. USA 94(22): 12,018–12, 023.
Wilson, C. A., L. Ramos, M. R. Villasenor, K. H. Anders, M. F. Press, K. Clarke, et al. 1999. Localization of human BRCA1 and its loss in high-grade, non-inherited breast carcinomas. Nature Genet. 21 (2): 236–240.
Xia, S. J., M. A. Shammas, and R. J. Shmookler Reis. 1997. Elevated recombination in immortal human cells is mediated by HsRAD51 recombinase. Mol. Cell. Biol. 17 (12): 7151–7158.
Xu, X., K. U. Wagner, D. Larson, Z. Weaver, C. Li, T. Ried, et al. 1999. Conditional mutation of Brcal in mammary epithelial cells results in blunted ductal morphogenesis and tumour formation. Nat. Genet. 22 (1): 37–43.
Xu, X., Z. Weaver, S. P. Linke, C. Li, J. Gotay, X. W. Wang, et al. 1999. Centrosome amplification and a defective G2-M cell cycle checkpoint induce genetic instability in BRCA1 exon 11 isoform-deficient cells. Mol. Cell 3 (3): 389–395.
Yu, G. L., and E. H. Blackburn. 1991. Developmentally programmed healing of chromosomes by telomerase in Tetrahymena. Cell 67 (4): 823–832.
Yu, G. L., J. D. Bradley, L. D. Attardi, and E. H. Blackburn. 1990. In vivo alteration of telomere sequences and senescence caused by mutated Tetrahymena telomerase RNAs. Nature 344 (6262): 126–132.
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Jasin, M. (2001). Double-Strand Break Repair and Homologous Recombination in Mammalian Cells. In: Nickoloff, J.A., Hoekstra, M.F. (eds) DNA Damage and Repair. Contemporary Cancer Research. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-095-7_9
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