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DNA Damage and Repair pp 147–172Cite as

The MRE11-RAD50 Complex

Diverse Functions in the Cellular DNA Damage Response

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Part of the book series: Contemporary Cancer Research ((CCR))

Abstract

In recent years, progress toward understanding the mechanisms and molecules with which mammalian cells respond to DNA double-strand breaks (DSBs) has been dramatic. This is attributable in part to the analysis of DSB repair-deficient rodent cell lines, which led to the isolation and characterization of the DNA-PK complex, XRCC4, DNA ligase IV, and others (3,43,49,59,60,79,83,100,103,112). The gene products thus identified have provided many important insights regarding the functions that maintain genomic integrity in the face of genotoxic stress. These studies have also shed light on DNA recombination pathways that diversify genetic information in the establishment of the immune repertoire. Nonetheless, the bulk of our current understanding of DNA recombination pathways has come from genetic and biochemical studies in Saccharomyces cerevisiae and bacterial systems. As an alternative to phenotype-driven analysis, a number of investigators have pursued the identification of mammalian counterparts to bacterial and S. cerevisiae recombinational DNA repair proteins to examine the cellular DNA damage response in mammals (46,80). The potential of this comparative approach has been most impressively realized in the functional analysis of the yeast and mammalian Rad51 proteins, which are homologs of the bacterial RecA protein (9,38,96). More recently, the MRE11-RAD50 protein complex, with homologs in bacteria, S. cerevisiae, and mammals, has emerged as a central player in the DNA transactions that preserve genomic integrity in yeast and mammalian cells.

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References

  1. Ajimura, M., S. H. Leem, and H. Ogawa. 1993. Identification of new genes required for meiotic recombination in Saccharomyces cerevisiae. Genetics 133: 51–66.

    PubMed  CAS  Google Scholar 

  2. Alani, E., R. Padmore, and N. Kleckner. 1990. Analysis of wild-type and rad50 mutants of yeast suggests an intimate relationship between meiotic chromosome synapsis and recombination. Cell 61: 419–436.

    Article  PubMed  CAS  Google Scholar 

  3. Albala, J. S., M. P. Thelen, C. Prange, W. Fan, M. Christensen, L. H. Thompson, and G. G. Lennon. 1997. Identification of a novel human RAD51 homolog, RAD51B. Genomics 46: 476–479.

    Article  PubMed  CAS  Google Scholar 

  4. Antoccia, A., R. Ricordy, R. Maraschio, S. Prudente, and C. Tanzarella. 1997. Chromosomal sensitivity to clastogenic agents and cell cycle perturbations in Nijmegen breakage syndrome lymphoblastoid cell lines. Int. J. Radiat. Biol. 71: 41–49.

    Article  PubMed  CAS  Google Scholar 

  5. Baumann, R, F. E. Benson, and S. C. West. 1996. Human Rad51 protein promotes ATP-dependent homologous pairing and strand transfer reactions in vitro. Cell 87: 757–766.

    Article  PubMed  CAS  Google Scholar 

  6. Bergerat, A., B. de Massy, D. Gadelle, R. C. Varoutas, A. Nicolas, and P. Forterre. 1997. An atypical topoisomerase II from Archaea with implications for meiotic recombination [see comments]. Nature 386: 414–417.

    Article  PubMed  CAS  Google Scholar 

  7. Besmer, E., J. Mansilla-Soto, S. Cassard, D. J. Sawchuk, G. Brown, M. Sadofsky, et al. 1998. Hairpin coding end opening is mediated by RAG1 and RAG2 proteins. Mol. Cell 2: 817–828.

    Article  PubMed  CAS  Google Scholar 

  8. Bhargava, J., J. Engebrecht, and G. S. Roeder. 1992. The rec102 mutant of yeast is defective in meiotic recombination and chromosome synapsis. Genetics 130: 59–69.

    PubMed  CAS  Google Scholar 

  9. Bianco, R. R., R. B. Tracy, and S. C. Kowalczykowski. 1998. DNA strand exchange proteins: a biochemical and physical comparison. Front. Biosci. 3: d570–603.

    PubMed  CAS  Google Scholar 

  10. Bork, R, K. Hofmann, P. Bucher, A. E Neuwald, S. F. Altschul, and E. V. Koonin. 1997. A superfamily of conserved domains in DNA damage-responsive cell cycle checkpoint proteins. Faseb J. 11: 68–76.

    PubMed  CAS  Google Scholar 

  11. Boulton, S. J., and S. R. Jackson. 1998. Components of the Ku-dependent non-homologous end-joining pathway are involved in telomeric length maintenance and telomeric silencing. EMBO J. 17: 1819–1828.

    Article  PubMed  CAS  Google Scholar 

  12. Boulton, S. J., and S. P. Jackson. 1996. Identification of a Saccharomyces cerevisiae Ku80 homologue: roles in DNA double strand break rejoining and in telomeric maintenance. Nucleic Acids Res. 24: 4639–4648.

    Article  PubMed  CAS  Google Scholar 

  13. Boulton, S. J., and S. R. Jackson. 1996. Saccharomyces cerevisiae Ku70 potentiates illegitimate DNA double-strand break repair and serves as a barrier to error-prone DNA repair pathways. Embo J. 15: 5093–5103.

    PubMed  CAS  Google Scholar 

  14. Bressan, D. A., B. K. Baxter, and J. H. J. Petrini. 1999. The Mrel l-Rad50-Xrs2 protein complex facilitates homologous recombination-based double-strand break repair in Saccharomyces cerevisiae. Mol. Cell. Biol. 19: 7681–7687.

    CAS  Google Scholar 

  15. Bressan, D. A., H. A. Olivares, B. E. Nelms, and J. H. J. Petrini. 1998. Alteration of N-terminal phosphoesterase signature motifs inactivates Saccharomyces cerevisiae Mrell. Genetics 150: 592–600.

    Google Scholar 

  16. Bressan, D. A., and J. H. J. Petrini. 1999. Unpublished results.

    Google Scholar 

  17. Bullard, S. A., S. Kim, A. M. Galbraith, and R. E. Malone. 1996. Double strand breaks at the HIS2 recombination hot spot in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 93: 13054–13059.

    Article  PubMed  CAS  Google Scholar 

  18. Callebaut, I., and J. P. Mornon. 1997. From BRCA1 to RAP1: a widespread BRCT module closely associated with DNA repair. FEBS Lett. 400: 25–30.

    Article  PubMed  CAS  Google Scholar 

  19. Cao, L., E. Alani, and N. Kleckner. 1990. A pathway for generation and processing of double-strand breaks during meiotic recombination in S. cerevisiae. Cell 61: 1089–1101.

    Article  PubMed  CAS  Google Scholar 

  20. Carney, J. P., R. S. Maser, H. Olivares, E. M. Davis, M. Le Beau, J. R. Yates, 3rd, et al. 1998. The hMrel 1 /hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell 93: 477–486.

    Article  PubMed  CAS  Google Scholar 

  21. Chen, J., D. P. Silver, D. Walpita, S. B. Cantor, A. F. Gazdar, G. Tomlinson, et al. 1998. Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells. Mol. Cell 2: 317–328.

    Article  PubMed  CAS  Google Scholar 

  22. Connelly, J. C., E. S. de Leau, E. A. Okely, and D. R. Leach. 1997. Overexpression, purification, and characterization of the SbcCD protein from Escherichia coli. J. Biol. Chem. 272: 19819–19826.

    Article  PubMed  CAS  Google Scholar 

  23. Connelly, J. C., and D. R. F. Leach. 1996. The sbcC and sbcD genes of Escherichia coli encode a nuclease involved in palindrome inviability and genetic recombination. Genes Cells 1: 285–291.

    Article  PubMed  CAS  Google Scholar 

  24. Cox, M. M. 1998. A broadening view of recombinational DNA repair in bacteria. Genes Cells 3: 65–78.

    Article  PubMed  CAS  Google Scholar 

  25. Critchlow, S. E., and S. P. Jackson. 1998. DNA end-joining: from yeast to man. Trends Biochem. Sci. 23: 394–398.

    Article  PubMed  CAS  Google Scholar 

  26. 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 hMrell: identification of a conserved multiprotein complex implicated in recombinational DNA repair. Mol. Cell. Biol. 16: 4832–4841.

    PubMed  CAS  Google Scholar 

  27. Furuse, M., Y. Nagase, H. Tsubouchi, K. Murakami-Murofushi, T. Shibata, and K. Ohta. 1998. Distinct roles of two separable in vitro activities of yeast Mrell in mitotic and meiotic recombination. EMBO J. 17: 6412–6425.

    Article  PubMed  CAS  Google Scholar 

  28. Game, J. C. 1993. DNA double strand breaks and the RAD5O-RAD57 genes in Saccharomyces. Cancer Biology 4: 73–83.

    CAS  Google Scholar 

  29. Game, J. C., and R. K. Mortimer. 1974. A genetic study of X-ray sensitive mutants in yeast. Mutat. Res. 24: 281–292.

    Article  PubMed  CAS  Google Scholar 

  30. Goldberg, J., H. B. Huang, Y. G. Kwon, P. Greengard, A. C. Nairn, and J. Kuriyan. 1995. Three-dimensional structure of the catalytic subunit of protein serine/threonine phosphatase-1. Nature 376: 745–753.

    Article  PubMed  CAS  Google Scholar 

  31. Griffith, J. P., J. L. Kim, E. E. Kim, M. D. Sintchak, J. A. Thomson, M. J. Fitzgibbon, et al. 1995. X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12–FK506 complex. Cell 82: 507–522.

    Article  PubMed  CAS  Google Scholar 

  32. Gupta, R. C., L. R. Bazemore, E. I. Golub, and C. M. Radding. 1997. Activities of human recombination protein Rad51. Proc. Natl. Acad. Sci. USA 94: 463–468.

    Article  PubMed  CAS  Google Scholar 

  33. Haaf, T., E. I. Golub, G. Reddy, C. M. Radding, and D. C. Ward. 1995. Nuclear foci of mammalian Rad51 recombination protein in somatic cells after DNA damage and its localization in synaptonemal complexes. Proc. Natl. Acad. Sci. USA 92: 2298–2302.

    Article  PubMed  CAS  Google Scholar 

  34. Haber, J. E. 1995. In vivo biochemistry: physical monitoring of recombination induced by site-specific endonucleases. Bioessays 17: 609–620.

    Article  PubMed  CAS  Google Scholar 

  35. Haber, J. E. 1998. The many interfaces of Mrell. Cell 95: 583–586.

    Article  PubMed  CAS  Google Scholar 

  36. Hernandez, D., C. M. McConville, M. Stacey, C. G. Woods, M. M. Brown, R. Shutt, et al. 1993. A family showing no evidence of linkage between the ataxia telangiectasia gene and chromosome 11g22–23. J. Med. Genet. 30: 135–140.

    Article  PubMed  CAS  Google Scholar 

  37. Hogan, B. 1994. Manipulating the Mouse Embryo: A Laboratory Manual, 2nd ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.

    Google Scholar 

  38. Ivanov, E. L., and J. E. Haber. 1997. DNA repair: RAD alert. Curr. Biol. 7: R492 - R495.

    CAS  Google Scholar 

  39. Ivanov, E. L., and J. E. Haber. 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.

    PubMed  CAS  Google Scholar 

  40. Ivanov, E. L., V. G. Korolev, and F. Fabre. 1992. XRS2, a DNA repair gene of Saccharomyces cerevisiae, is needed for meiotic recombination. Genetics 132: 651–664.

    CAS  Google Scholar 

  41. Ivanov, E. L., N. Sugawara, J. Fishman-Lobell, and J. E. Haber. 1996. Genetic requirements for the single-strand annealing pathway of double-strand break repair in Saccharomyces cerevisiae. Genetics 142: 693–704.

    CAS  Google Scholar 

  42. Ivanov, E. L., N. Sugawara, C. I. White, F. Fabre, and J. E. Haber. 1994. Mutations in XRS2 and RAD50 delay but do not prevent mating-type switching in Saccharomyces cerevisiae. Mol. Cell. Biol. 14: 3414–3425.

    PubMed  CAS  Google Scholar 

  43. Jeggo, P. A., G. E. Taccioli, and S. P. Jackson. 1995. Menage a trois: double strand break repair, V(D)J recombination and DNA-PK. Bioessays 17: 949–957.

    Article  PubMed  CAS  Google Scholar 

  44. Johzuka, K., and H. Ogawa. 1995. Interaction of Mre 11 and Rad50: Two proteins required for DNA repair and Meiosis-specific double-strand break formation in Saccharamoyces cerevisiae. Genetics 139: 1521–1532.

    CAS  Google Scholar 

  45. Jongmans, W., M. Vuillaume, K. Chrzanowska, D. Smeets, K. Sperling, and J. Hall. 1997. Nijmegen breakage syndrome cells fail to induce the p53-mediated DNA damage response following exposure to ionizing radiation. Mol. Cell. Biol. 17: 5016–5022.

    PubMed  CAS  Google Scholar 

  46. Kanaar, R., and J. H. J. Hoeijmakers. 1997. Recombination and joining: different means to the same ends. Genes Function 1: 165–174.

    Article  CAS  Google Scholar 

  47. Keeney, S., C. N. Giroux, and N. Kleckner. 1997. Meiosis-specific DNA double-strand breaks are catalyzed by Spol 1, a member of a widely conserved protein family. Cell 88: 375–384.

    Article  PubMed  CAS  Google Scholar 

  48. Keeney, S., and N. Kleckner. 1995. Covalent protein-DNA complexes at the 5’ strand termini of meiosis-specific double-strand breaks in yeast. Proc. Natl. Acad. Sci. USA 92: 11274–11278.

    Article  PubMed  CAS  Google Scholar 

  49. Kirchgessner, C. U., C. K. Patil, J. W. Evans, C. A. Cuomo, L. M. Fried, T. Carter, et al. 1995. DNA-dependent kinase (p350) as a candidate gene for the murine SCID defect. Science 267: 1178–1183.

    Article  PubMed  CAS  Google Scholar 

  50. Kironmai, K. M., and K. Muniyappa. 1997. Alteration of telomeric sequences and senescence caused by mutations in RAD50 of Saccharomyces cerevisiae. Genes Cells 2: 443–455.

    Article  PubMed  CAS  Google Scholar 

  51. Klapholz, S., and R. E. Esposito. 1980. Recombination and chromosome segregation in during the single division meosis in spo12–1 and spo13–1 diploids. Genetics 96: 589–611.

    PubMed  CAS  Google Scholar 

  52. Kleckner, N. 1996. Meiosis: how could it work? Proc. Natl. Acad. Sci. USA 93: 8167–8174.

    Article  PubMed  CAS  Google Scholar 

  53. Le Beau, M. 1999. personal communication.

    Google Scholar 

  54. Leach, D. R. 1994. Long DNA palindromes, cruciform structures, genetic instability and secondary structure repair. Bioessays 16: 893–900.

    Article  PubMed  CAS  Google Scholar 

  55. Leach, D. R. F., R. G. Lloyd, and A. F. W. Coulson. 1992. The SbcCD protein of Escherichia coli is related to two putative nucleases in the UvrA superfamily of nucleotide-binding proteins. Genetica 87: 95–100.

    Article  PubMed  CAS  Google Scholar 

  56. Lee, S. E., J. K. Moore, A. Holmes, K. Umezu, R. D. Kolodner, and J. E. Haber. 1998. Saccharomyces Ku70, mrell/rad50 and RPA proteins regulate adaptation to G2/M arrest after DNA damage. Cell 94: 399–409.

    Article  PubMed  CAS  Google Scholar 

  57. Lewis, S. M. 1994. P nucleotides, hairpin DNA and V (D) J joining: making the connection. Semin. Immunol. 6: 131–141.

    CAS  Google Scholar 

  58. Lichten, M., and A. S. Goldman. 1995. Meiotic recombination hotspots. Annu. Rev. Genet. 29: 423–444.

    Article  PubMed  CAS  Google Scholar 

  59. 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.

    Article  PubMed  CAS  Google Scholar 

  60. Liu, N., J. E. Lamerdin, J. D. Tucker, Z. Q. Zhou, C. A. Walter, J. S. Albala, et al. 1997. The human XRCC9 gene corrects chromosomal instability and mutagen sensitivities in CHO UV40 cells. Proc. Natl. Acad. Sci. USA 94: 9232–9237.

    Article  PubMed  CAS  Google Scholar 

  61. Luo, G., M. S. Yao, C. F. Bender, M. Mills, A. R. Bladl, A. Bradley, and J. H. Petrini. 1999. Disruption of mRad50 causes embryonic stem cell lethality, abnormal embryonic development, and sensitivity to ionizing radiation. Proc. Natl. Acad. Sci. USA 96: 7376–7381.

    Article  PubMed  CAS  Google Scholar 

  62. Malone, R. E., T. Ward, S. Lin, and J. Waring. 1990. The RAD50 gene, a member of the double strand break repair epistasis group, is not required for spontaneous mitotic recombination in yeast. Curr. Genet. 18: 111–116.

    Article  PubMed  CAS  Google Scholar 

  63. Maser, R., and J. H. J. Petrini. 1999. Unpublished results.

    Google Scholar 

  64. Maser, R. S., K. J. Monsen, B. E. Nelms, and J. H. J. Petrini. 1997. hMrel 1 and hRad50 nuclear foci are induced during the normal cellular response to DNA double strand breaks. Mol. Cell. Biol. 17: 6087–6096.

    Google Scholar 

  65. Matsuura, K., T. Balmukhanov, H. Tauchi, C. Weemaes, D. Smeets, K. Chrzanowska, et al. 1998. Radiation induction of p53 in cells from Nijmegen breakage syndrome is defective but not similar to ataxia-telangiectasia. Biochem. Biophys. Res. Commun. 242: 602–607.

    Article  PubMed  CAS  Google Scholar 

  66. Matsuura, S., H. Tauchi, A. Nakamura, N. Kondo, S. Sakamoto, S. Endo, et al. 1998. Positional cloning of the gene for Nijmegen breakage syndrome. Nature Genet. 19: 179–181.

    Article  PubMed  CAS  Google Scholar 

  67. Milne, G. T., S. Jin, K. B. Shannon, and D. T. Weaver. 1996. Mutations in two Ku homologs define a DNA end joining repair pathway in Saccharomyces cerevisiae. Mol. Cell. Biol. 16: 4189–4198.

    CAS  Google Scholar 

  68. Moore, J. K., and J. E. Haber. 1996. Cell cycle and genetic requirements of two pathways of nonhomologous end joining repair of double-strand breaks in Saccharomyces cerevisiae. Mol. Cell. Biol. 16: 2164–2173.

    PubMed  CAS  Google Scholar 

  69. Moreau, S., J. R. Ferguson, and L. S. Symington. 1999. The nuclease activity of mrell is required for meiosis but not for mating type switching, end joining, or telomere maintenance. Mol. Cell. Biol. 19: 556–566.

    PubMed  CAS  Google Scholar 

  70. Nairz, K., and F. Klein. 1997. mrelis: a yeast mutation that blocks double-strand-break processing and permits nonhomologous synapsis in meiosis. Genes Dev. 11: 2272–2290.

    Google Scholar 

  71. Nelms, B. E., R. S. Maser, J. F. MacKay, M. G. Lagally, and J. H. J. Petrini. 1998. In situ visualization of DNA double-strand break repair in human fibroblasts. Science 280: 590–592.

    Article  PubMed  CAS  Google Scholar 

  72. Nove, J., J. B. Little, P. J. Mayer, P. Troilo, and W. W. Nichols. 1986. Hypersensitivity of cells from a new chromosomal-breakage syndrome to DNA-damaging agents. Mutat. Res. 163: 255–262.

    Article  PubMed  CAS  Google Scholar 

  73. Nugent, C. I., G. Bosco, L. O. Ross, S. K. Evans, A. P. Salinger, J. K. Moore, et al. 1998. Telomere maintenance is dependent on activities required for end repair of double-strand breaks. Curr. Biol. 8: 657–660.

    Article  PubMed  CAS  Google Scholar 

  74. Ogawa, H., K. Johzuka, T. Nakagawa, S. Leem, and A. Hagihara. 1995. Functions of the yeast meiotic recombination genes, MRE1 1 and MRE2. Adv. Biophys. 31: 67–76.

    Article  PubMed  CAS  Google Scholar 

  75. Ohta, K., A. Nicolas, M. Furuse, A. Nabetani, H. Ogawa, and T. Shibata. 1998. Mutations in the MRE11, RAD50, XRS2, and MRE2 genes alter chromatin configuration at meiotic DNA double-stranded break sites in premeiotic and meiotic cells. Proc. Natl. Acad. Sci. USA 95: 646–651.

    Article  PubMed  CAS  Google Scholar 

  76. Painter, R. B. 1981. Radioresistant DNA synthesis: an intrinsic feature of ataxia telangiectasia. Mutat. Res. 84: 183–190.

    Article  PubMed  CAS  Google Scholar 

  77. 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: 969–979.

    Article  PubMed  CAS  Google Scholar 

  78. Paulovich, A. G., D. P. Toczyski, and L. H. Hartwell. 1997. When checkpoints fail. Cell 88: 315–321.

    Article  PubMed  CAS  Google Scholar 

  79. Peterson, S. R., A. Kurimasa, M. Oshimura, W. S. Dynan, E. M. Bradbury, and D. J. Chen. 1995. Loss of the catalytic subunit of the DNA-dependent protein kinase in DNA doublestrand-break-repair mutant mammalian cells. Proc. Natl. Acad. Sci. USA 92: 3171–3174.

    Article  PubMed  CAS  Google Scholar 

  80. Petrini, J. H., D. A. Bressan, and M. S. Yao. 1997. The RAD52 epistasis group in mammalian double strand break repair. Semin. Immunol. 9: 181–188.

    Article  PubMed  CAS  Google Scholar 

  81. Petrini, J. H. J., M. E. Walsh, C. Di Mare, J. R. Korenberg, X. -N. Chen, and D. T. Weaver. 1995. Isolation and Characterization of the Human MREll homologue. Genomics 29: 80–86.

    Article  PubMed  CAS  Google Scholar 

  82. Porter, S. E., P. W. Greenwell, K. B. Ritchie, and T. D. Petes. 1996. The DNA-binding protein Hdf 1 p (a putative Ku homologue) is required for maintaining normal telomere length in Saccharomyces cerevisiae. Nucleic Acids Res. 24: 582–585.

    Article  PubMed  CAS  Google Scholar 

  83. Rathmell, W. K., and G. Chu. 1994. Involvement of the Ku autoantigen in the cellular response to DNA double-strand breaks. Proc. Natl. Acad. Sci. USA 91: 7623–7627.

    Article  PubMed  CAS  Google Scholar 

  84. Raymond, W. E., and N. Kleckner. 1993. RAD50 protein of S. cerevisiae exhibits ATP-dependent DNA binding. Nucleic Acids Res. 21: 3851–3856.

    Article  PubMed  CAS  Google Scholar 

  85. Riballo, E., S. E. Critchlow, S.-H. Teo, A. J. Doherty, A. Priestley, B. Broughton, et al. 1999. Identification of a defect in DNA ligase IV in a radiosensitive leukaemia patient. Curr. Biol. 9: 699–702.

    Article  PubMed  CAS  Google Scholar 

  86. Roeder, G. S. 1997. Meiotic chromosomes: it takes two to tango. Genes Dey. 11: 2600–2621.

    Article  CAS  Google Scholar 

  87. Saeki, T., I. Machida, and S. Nakai. 1980. Genetic control of diploid recovery after y-irradiation in the yeast Saccharomyces cerevisiae. Mutat. Res. 73: 251–265.

    Article  CAS  Google Scholar 

  88. Santocanale, C., and J. F. Diffley. 1998. A Mec1- and Rad53-dependent checkpoint controls late-firing origins of DNA replication. Nature 395: 615–618.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  90. Schiestl, R. H., and T. D. Petes. 1991. Integration of DNA fragments by illegitimate recombination in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 88: 7585–7589.

    Article  PubMed  CAS  Google Scholar 

  91. Schiestl, R. H., J. Zhu, and T. D. Petes. 1994. Effect of mutations in genes affecting homologous recombination on restriction enzyme-mediated and illegitimate recombination in Saccharomyces cerevisae. Mol. Cell. Biol. 14: 4495–4500.

    Google Scholar 

  92. Scully, R., J. Chen, A. Plug, Y. Xiao, D. Weaver, J. Feunteun, et al. 1997. Association of BRCA1 with Rad51 in mitotic and meiotic cells. Cell 88: 265–275.

    Article  PubMed  CAS  Google Scholar 

  93. Seemanova, E. 1990. An increased risk for malignant neoplasms in heterozygotes for a syndrome of microcephaly, normal intelligence, growth retardation, remarkable facies, immunodeficiency and chromosomal instability. Mutat. Res. 238: 321–324.

    Article  PubMed  CAS  Google Scholar 

  94. Sharpies, G. J., and D. R. Leach. 1995. Structural and functional similarities between the SbcCD proteins of Escherichia coli and the RAD50 and MRE11 (RAD32) recombination and repair proteins of yeast. Mol. Microbiol. 17: 1215–1217.

    Article  Google Scholar 

  95. Shiloh, Y. 1997. Ataxia-telangiectasia and the Nijmegen breakage syndrome: related disorders but genes apart. Annu. Rev. Genet. 31: 635–662.

    Article  PubMed  CAS  Google Scholar 

  96. Shinohara, A., and T. Ogawa. 1995. Homologous recombination and the roles of double-strand breaks. Trends Biochem. Sci. 20: 387–391.

    Article  PubMed  CAS  Google Scholar 

  97. Shirahige, K., Y. Hori, K. Shiraishi, M. Yamashita, K. Takahashi, C. Obuse, et al. 1998. Regulation of DNA-replication origins during cell-cycle progression. Nature 395: 618–621.

    Article  PubMed  CAS  Google Scholar 

  98. Stewart, G. S., R. S. Maser, T. Stankovic, D. A. Bressan, M. I. Kaplan, N. G. J. Jaspers, et al. 1999. The DNA double strand break repair gene hMre11 is mutated in individuals with an ataxia telangiectasia-like disorder (ATLD). Cell 99: 577–587.

    Article  PubMed  CAS  Google Scholar 

  99. Taalman, R. D., N. G. Jaspers, J. M. Scheres, J. de Wit, and T. W. Hustinx. 1983. Hypersensitivity to ionizing radiation, in vitro, in a new chromosomal breakage disorder, the Nijmegen Breakage Syndrome. Mutat. Res. 112: 23–32.

    Article  PubMed  CAS  Google Scholar 

  100. Taccioli, G. E., T. M. Gottlieb, T. Blunt, A. Priestley, J. Demengeot, R. Mizuta, et al. 1994. Ku80: Product of the XRCC5 gene and its role in DNA repair and V (D) J recombination. Science 265: 1442–1445.

    CAS  Google Scholar 

  101. Tashiro, S., N. Kotomura, A. Shinohara, K. Tanaka, K. Ueda, and N. Kamada. 1996. S phase specific formation of the human Rad51 protein nuclear foci in lymphocytes. Oncogene 12: 2165–2170.

    PubMed  CAS  Google Scholar 

  102. Teo, S. H., and S. P. Jackson. 1997. Identification of Saccharomyces cerevisiae DNA ligase IV: involvement in DNA double-strand break repair. EMBO J. 16: 4788–4795.

    Article  PubMed  CAS  Google Scholar 

  103. Thompson, L. H., K. W. Brookman, N. J. Jones, S. A. Allen, and A. V. Carrano. 1990. Molecular cloning of the human XRCC1 gene, which corrects defective DNA strand break repair and sister chromatid exchange. Mol. Cell. Biol. 10: 6160–6171.

    PubMed  CAS  Google Scholar 

  104. Toczyski, D. P., D. J. Galgoczy, and L. H. Hartwell. 1997. CDC5 and CKII control adaptation to the yeast DNA damage checkpoint. Cell 90: 1097–1106.

    Article  PubMed  CAS  Google Scholar 

  105. Trujillo, K. M., S. S. F. Yuan, E. Lee, and R. Sung. 1998. Nuclease activities in a complex of human recombination and DNA repair factors rad50, mrel 1, and p95 In Process Citation]. J. Biol. Chem. 273: 21447–21450.

    Article  PubMed  CAS  Google Scholar 

  106. Tsubouchi, H., and H. Ogawa. 1998. A novel mrel 1 mutation impairs processing of double-strand breaks of DNA during both mitosis and meiosis. Mol. Cell. Biol. 18: 260–268.

    PubMed  CAS  Google Scholar 

  107. Tsukamoto, Y., and H. Ikeda. 1998. Double-strand break repair mediated by DNA end-joining. Genes Cells 3: 135–144.

    Article  PubMed  CAS  Google Scholar 

  108. Tsukamoto, Y., J. Kato, and H. Ikeda. 1997. Budding yeast Rad50, Mrel 1, Xrs2, and Hdfl, but not Rad52, are involved in the formation of deletions on a dicentric plasmid. Mol. Gen. Genet. 255: 543–547.

    Article  PubMed  CAS  Google Scholar 

  109. Usui, T., T. Ohta, H. Oshiumi, J. Tomizawa, H. Ogawa, and T. Ogawa. 1998. Complex formation and functional versatility of Mrel 1 of budding yeast in recombination. Cell 95: 705–716.

    Article  PubMed  CAS  Google Scholar 

  110. van der Burgt, I., K. H. Chrzanowska, D. Smeets, and C. Weemaes. 1996. Nijmegen breakage syndrome. J. Med. Genet. 33: 153–156.

    Article  PubMed  Google Scholar 

  111. 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: 467–476.

    Article  PubMed  CAS  Google Scholar 

  112. Weaver, D. T. 1995. What to do at an end: DNA double-strand break repair. Trends Genet. 11: 388–392.

    Article  PubMed  CAS  Google Scholar 

  113. Weiner, B. M., and N. Kleckner. 1994. Chromosome pairing via multiple interstitial interactions before and during meiosis in yeast. Cell 77: 977–991.

    Article  PubMed  CAS  Google Scholar 

  114. White, C. I., and J. E. Haber. 1990. Intermediates of recombination during mating type switching in Saccharomyces cerevisiae. EMBO J. 9: 663–673.

    PubMed  CAS  Google Scholar 

  115. Wilson, T. E., U. Grawunder, and M. R. Lieber. 1997. Yeast DNA ligase IV mediates non-homologous DNA end joining. Nature 388: 495–498.

    Article  PubMed  CAS  Google Scholar 

  116. Xiao, Y., and D. T. Weaver. 1997. Conditional gene targeted deletion by Cre recombinase demonstrates the requirement for the double-strand break repair Mrel1 protein in murine embryonic stem cells. Nucleic Acids Res. 25: 2985–2991.

    Article  PubMed  CAS  Google Scholar 

  117. Yamaguchi-Iwai, Y., E. Sonoda, M. S. Sasaki, C. Morrison, T. Haraguchi, Y. Hiraoka, et al. 1999. Mre11 is essential for the maintenance of chromosomal DNA in vertebrate cells. EMBO J. 18: 6619–6629.

    Article  PubMed  CAS  Google Scholar 

  118. Yamazaki, V., R. D. Wegner, and C. U. Kirchgessner. 1998. Characterization of cell cycle checkpoint responses after ionizing radiation in Nijmegen breakage syndrome cells. Cancer Res. 58: 2316–2322.

    PubMed  CAS  Google Scholar 

  119. Zhuo, S., J. C. Clemens, D. J. Hakes, D. Barford, and J. E. Dixon. 1993. Expression, purification, crystallization, and biochemical characterization of a recombinant protein phosphatase. J. Biol. Chem. 268: 17,754–17, 761.

    Google Scholar 

  120. Zhuo, S., J. C. Clemens, R. L. Stone, and J. E. Dixon. 1994. Mutational analysis of a Ser/Thr phosphatase. J. Biol. Chem. 269: 26234–26238.

    PubMed  CAS  Google Scholar 

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Authors
  1. John H. J. Petrini
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  2. Richard S. Maser
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  3. Debra A. Bressan
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Editors and Affiliations

  1. Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM, USA

    Jac A. Nickoloff

  2. Qbiogene, Carlsbad, CA, USA

    Merl F. Hoekstra

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© 2001 Humana Press Inc., Totowa, NJ

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Petrini, J.H.J., Maser, R.S., Bressan, D.A. (2001). The MRE11-RAD50 Complex. 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_7

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  • DOI: https://doi.org/10.1007/978-1-59259-095-7_7

  • Publisher Name: Humana Press, Totowa, NJ

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