Advertisement

Multiple Guardians of the Epithelial Stage IV Meiotic Checkpoint

  • T. Ashley
Conference paper
Part of the Ernst Schering Research Foundation Workshop book series (SCHERING FOUND, volume 9)

Abstract

Cell cycle checkpoints and checkpoint proteins monitor the condition of the DNA and chromosomes as they proceed through their appointed rounds (Hartwell and Weinert 1989). “Monitoring” includes detecting irregularities, such as replication arrest, DNA lesions or chromosomes unattached to the spindle. Once an abnormality has been detected, the damage surveillance network of cell cycle proteins halts cell cycle progression until the error is rectified, or shunts the cell into an apoptotic pathway. The location and function of somatic cell cycle checkpoints have been the subject of extensive investigations and are well defined (Murray and Hunt 1993; Weinert and Lydall 1993; Elledge 1996; Hoekstra 1997; Weinert 1997; Stillman 1999). They include a G1 checkpoint, an intra-S checkpoint, a G2 checkpoint and an M checkpoint. The G1 checkpoint assures that there is no unrepaired damage to the DNA as the cell begins to replicate and the checkpoint proteins set in motion replication of genes required for DNA synthesis. Similarly the G2 checkpoint ensures that there is no unrepaired damage as the cell prepares to divide. The intra S checkpoint monitors both progression of DNA replication and any DNA damage such as double strand breaks (DSBs). In the event of a break, the intra S checkpoint halts replication until repair is completed. In contrast to the other checkpoints, the M checkpoint is a spindle checkpoint that assures all the chromosomes are attached to the spindle and oriented to opposite poles. If an error in a somatic cell cannot be remedied, eliminating the cell prevents the perpetuation of the error. The same is true in meiotic cells. However, if the error is due to a mutation in a critical gene required for meiosis and all the affected spermatocytes undergo apoptosis, the consequence is male sterility (see (Ashley 2000) for a recent review).

Keywords

Cell Cycle Checkpoint Meiotic Prophase Ataxia Telangiectasia RecA Protein Nijmegen Breakage Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aguilera, A. (2001). “Double-strand break repair: are Rad5l/RecA—DNA joints barriers to DNA replication?” Trends Genet 17: 318–321.PubMedCrossRefGoogle Scholar
  2. Alani, E., R. Padmore, et al. (1990). “Analysis of wild-type and rad50 mutants of yeast suggests an intimate relationship between meiotic chromosome synapsis and recombination.” Cell 61: 419–436.PubMedCrossRefGoogle Scholar
  3. Allers, T. and M. Lichten (2001). “Differential timing and control of noncrossover and crossover recombination during meiosis.” Cell 106: 47–57.PubMedCrossRefGoogle Scholar
  4. Ashley, T. (2000). An integration of old and new perspectives of mammalian meiotic sterility. Results and Problems in Cell Differentiation: The Genetic Basis of Male Infertility. K. McEcelreay. Berlin, Heidelberg, Springer-Verlag. 28: 131–173.Google Scholar
  5. Ashley, T. and A. W. Plug (1998). Caught in the act: deducing meiotic function from protein immunolocalization. Current Topics in Dev Biol. M. A. Handel, Academic Press. 37: 201–239.Google Scholar
  6. Baker, S. M., A. W. Plug, et al. (1996). “Involvement of mouse Mlhl in DNA mismatch repair and meiotic crossing over.” Nat Genet 13: 336–342.PubMedCrossRefGoogle Scholar
  7. Barlow, C., S. Hirotsune, et al. (1996). “ATM-deficient mice: a paradigm of ataxia telangiectasia.” Cell 86: 159–171.PubMedCrossRefGoogle Scholar
  8. Barlow, C., M. Liyanage, et al. (1997). “Partial rescue of the prophase I defect of Atm-deficient mice by p53 and p21 null alleles.” Nat Genet 17: 462–466.PubMedCrossRefGoogle Scholar
  9. Bishop, D. K., D. Park, et al. (1992). “DMC1: a meiotic specific yeast homolog of E. coli rec A required for recombination, synaptonemal complex formation and cell cycle progression.” Cell 69: 439–456.PubMedCrossRefGoogle Scholar
  10. Bressan, D. A., B. K. Baxter, et al. (1999). “The Mre1l-Rad50-Xrs2 protein complex facilitates homologous recombination-based double-strand break repair in Saccharomyces cerevisiae.” Mol Cell Biol 19: 7681–7687.PubMedGoogle Scholar
  11. Brown, E. J. and D. Baltimore (2000). “ATR disruption leads to chromosomal fragmentation and early embryonic lethality.” Genes Dev 15: 397–402.Google Scholar
  12. Cao, L., E. Alani, et al. (1990). “A pathway for generation and processing of double-strand breaks during meiotic recombination in S. cerevisiae.” Cell 61: 1089–1101.PubMedCrossRefGoogle Scholar
  13. Carney, J. P., R. S. Maser, et al. (1998). “The hMre l l /hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response.” Cell 93: 477–486.PubMedCrossRefGoogle Scholar
  14. Chamankahah, M. and W. Xiao (1999). “Formation of the yeast Mrel l-Rad50Xrs2 complex is correlated with DNA repair and telomere maintenance.” Nucl Acid Res 27: 2072–2079.CrossRefGoogle Scholar
  15. Chen, J., D. P. Silver, et al. (1998). “Stable interactions between the products of the BRCAland BRCA2 tumor suppressor genes in mitotic and meiotic cells.” Molec Cell 2: 317–328.PubMedCrossRefGoogle Scholar
  16. Chen, J. J., D. P. Silver, et al. (1999). “BRCA1, BRCA2, and Rad51 operate in a common damage response pathway.” Cancer Res 57: 1752–1756.Google Scholar
  17. Chen, P., C. F. Chen, et al. (1998). “The BRC repeats in BRCA2 are critical for RAD51 binding and resistance to methyl methanesulfonate treatment.” Proc Natl Acad Sci USA 95: 5287–5292.PubMedCrossRefGoogle Scholar
  18. Cimprich, K. A., T. B. Shin, et al. (1996). “DNA cloning and gene mapping of a candidate human cell cycle checkpoint protein.” Proc Natl Acad Sci USA 93: 2850–2855.PubMedCrossRefGoogle Scholar
  19. Cortez, D., Y. Wang, et al. (1999). “Requirement of ATM-dependent phosphorylation of BRCAI in the DNA damage response to double-strand breaks.” Science 286: 1162–1166.PubMedCrossRefGoogle Scholar
  20. Courcelle, J. and P. C. Hanawalt (2001). “Participation of recombination proteins in rescue of arrested replication forks in UV-irradiated Escherichia coli need not involve recombination.” Proc Natl Acad Sci USA 98: 8196–8202.PubMedCrossRefGoogle Scholar
  21. Coverley, D. and R. A. Laskey (1994). “Regulation of eukaryotic DNA replication.” Annu Rev Biochem 63: 745–776.PubMedCrossRefGoogle Scholar
  22. D’Amours, D. and S. P. Jackson (2001). “The yeast Xrs2 complex functions in S phase checkpoint regulation.” Genes Dey 15: 2238–2249.CrossRefGoogle Scholar
  23. de Rooij, D. G. and J. A. Grootegoed (1998). “Spermatogonial stem cells.” Curr Opin Cell Biol 10: 694–701.PubMedCrossRefGoogle Scholar
  24. de Vries, S. S., E. B. Baart, et al. (1999). “Mouse MutS-like protein MSH5 is required for proper chromosome synapsis in male and female meiosis.” Genes Dey 13: 523–531.CrossRefGoogle Scholar
  25. Digweed, M., A. Reis, et al. (1999). “Nijmegen breakage syndrome: consequences of defective DNA double-strand break repair.” Bioessays 21: 649–656.PubMedCrossRefGoogle Scholar
  26. Edelmann, W., P. E. Cohen, et al. (1999). “Mammalian MutS homolgue 5 is required for chromosome pairing in meiosis.” Nat Genet 21: 123–127.PubMedCrossRefGoogle Scholar
  27. Eijpe, M., H. Offenberg, et al. (2000). “Localization of Rad50 and MRE1 1 in spermatocyte nuclei of mouse and rat.” Chromosoma 109: 123–132.PubMedCrossRefGoogle Scholar
  28. Elledge, S. J. (1996). “Cell cycle checkpoints: preventing an identity crisis.” Science 274: 1664–1672.PubMedCrossRefGoogle Scholar
  29. Gatei, M., S. R. Scott, et al. (2000). “Role for ATM in DNA damage-induced phosphorylation of BRCA 1.” Cancer Res 60: 3299–3304.PubMedGoogle Scholar
  30. Goedecke, W., M. Eijpe, et al. (1999). “MREI and Ku70 interact in somatic cells, but are differentially expressed in early meiosis.” Nat Genet 23: 194–198.PubMedCrossRefGoogle Scholar
  31. Gowen, L. C., B. L. Johnson, et al. (1996). “Brcal deficiency results in early embryonic lethality characterized by neuroepithelial abnormalities.” Nat Genet 12: 191–194.PubMedCrossRefGoogle Scholar
  32. Grenon, M., C. Gilbert, et al. (2001). “Checkpoint activation in response to double-strand breaks requires the Mrell/Rad50/Xrs2 complex.” Nat Cell Biol 3: 844–847.PubMedCrossRefGoogle Scholar
  33. Hartwell, L. H. and T. A. Weinert (1989). “Checkpoints: controls that ensure the order of cell cycle events.” Science 249: 629–634.CrossRefGoogle Scholar
  34. Hoekstra, M. F. (1997). “Responses to DNA damage and regulation of cell cycle checkpoints by the ATM protein kinase family.” Curr Op in Gen Dev 7: 170–175.CrossRefGoogle Scholar
  35. Hollingsworth, N. M., L. Ponte, et al. (1995). “MSH5, a novel MutS homolog, facilitates meiotic reciprocal recombination between homologs in Saccharomyces cerevisiae but not mismatch repair.” Genes Dev 9: 1728–1739.PubMedCrossRefGoogle Scholar
  36. Hotta, Y., M. Ito, et al. (1966). “Synthesis of DNA during meiosis.” Proc Natl Acad Sci USA 56: 1184–1191.PubMedCrossRefGoogle Scholar
  37. Hotta, Y. and H. Stern (1971). “Analysis of DNA synthesis during meiotic prophase in Lilium.” J Mol Biol 55: 337–355.PubMedCrossRefGoogle Scholar
  38. Hunter, N. and R. H. Borts (1997). “Mlhl is unique among mismatch repair proteins in its ability to promote crossing-over during meiosis.” Genes Dev 11: 1573–1582.PubMedCrossRefGoogle Scholar
  39. Hunter, N. and N. Kleckner (2001). Cell 106: 59–70.PubMedCrossRefGoogle Scholar
  40. Iftode, C., Y. Daniely, et al. (1999). “Replication protein A (RPA): the eukaryotic SSB.” Grit Rev Biochem Mol Biol 34: 141–180.CrossRefGoogle Scholar
  41. Ito, A., H. Tauchi, et al. (1999). “Expression of full-length NBSI protein restores normal radiation responses in cells from Nijmegen breakage syndrome patients.” Biochem Biophys Res Commun 265: 716–721.PubMedCrossRefGoogle Scholar
  42. Ito, M., Y. Hotta, et al. (1967). “Studies of meiosis in vitro. II. Effect of inhibiting DNA synthesis during meiotic prophase on chromosome structure and behavior.” Dev Biol 16: 54–77.PubMedCrossRefGoogle Scholar
  43. Ivanov, E. L., V. G. Korolev, et al. (1992). “XRS2, a DNA repair gene of Saccharomyces cerevisiae, is needed for meiotic recombination.” Genetics 132: 651–664.PubMedGoogle Scholar
  44. Johzuka, K. and H. Ogawa (1995). “Interaction of mrell and Rad50: two proteins required for DNA repair and meiosis-specific double-strand break formation in Saccharomyces cerevisiae.” Genetics 139: 1521–1532.PubMedGoogle Scholar
  45. Keegan, K. S., D. A. Holtzman, et al. (1996). “The ATR and ATM protein kinases associate with different sites along meiotically pairing chromosomes.” Genes Dev 10: 2423–2437.PubMedCrossRefGoogle Scholar
  46. Kleckner, N., R. Padmore, et al. (1991). “Meiotic chromosome metabolism: one view.” Cold Spring Harbor Symp Quant Biol 56: 729–743.PubMedCrossRefGoogle Scholar
  47. Kleckner, N. and B. M. Weiner (1993). “Potential advantages of unstable interactions for pairing of chromosomes in mitotic, somatic and premeiotic cells.” Cold Spring Harbor Symp Quant Biol 58: 553–565.PubMedCrossRefGoogle Scholar
  48. Kowalczykowski, S. C. (1991). “Biochemical and biological function of Escheria coli RecA protein: behavior of mutant RecA proteins.” Biochimie 73: 289–304.PubMedCrossRefGoogle Scholar
  49. Kuzminov, A. (2001). “DNA replication meets genetic exchange: chromosomal damage and its repair by homologous recombination.” Proc Natl Acad USA 98: 8461–8468.CrossRefGoogle Scholar
  50. Lavin, M. F. and K. K. Khanna (1999). “ATM: the protein encoded by the gene mutated in the radiosensitive syndrome ataxia-telangiectasia. ” Int J Radiat Biol 75: 1201–1214.PubMedCrossRefGoogle Scholar
  51. Lim, D.-S. and P. Hasty (1996). “A mutation in mouse rad51 results in an early embryonic lethal that is suppressed by a p53 mutation.” Mol Cell Biol 16: 7133–7143.PubMedGoogle Scholar
  52. Lim, D. S., S. T. Kim, et al. (2000). “ATM phosphorylates p95/Nbsl in an S-phase checkpoint pathway.” Nature 404: 613–617.PubMedCrossRefGoogle Scholar
  53. Liu, C.-Y., A. Flesken-Nikitin, et al. (1996). “Inactivation of the mouse Brcal gene leads to failure in the morphogenesis of the egg cylinder in early postimplantation development.” Genes Dev 10: 1835–1843.PubMedCrossRefGoogle Scholar
  54. Loidl, J., F. Klein, et al. (1994). “Homologous pairing is reduced but not abolished in asynaptic mutants of yeast.” J Cell Biol 125: 1191–1200.PubMedCrossRefGoogle Scholar
  55. Ludwig, T., D. L. Chapman, et al. (1997). “Targeted mutations of breast cancer susceptibility gene homologs in mice: lethal phenotypes of Brcal, Brca2, Brcal/Brca2, Brcal/p53, and Brca2/p53 nullizygous embryos.” Genes Dev 11: 1226–1241.PubMedCrossRefGoogle Scholar
  56. Luo, G. B., M. S. Yao, et al. (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.PubMedCrossRefGoogle Scholar
  57. Meyn, M. S. (1995). “Ataxia-telangiectasia and cellular responses to DNA damage.” Cancer Res 55: 5991–6001.PubMedGoogle Scholar
  58. Mizuta, R., J. M. LaSalle, et al. (1997). “RAB22 and RAB163/mouse BRCA2: proteins that specifically interact with the RADS I protein. ” Proc Natl Acad Sci USA 94: 6927–6932.PubMedCrossRefGoogle Scholar
  59. Murray, A. W. and T. Hunt (1993). The Cell Cycle: An Introduction. New York, Oxford University Press.Google Scholar
  60. Nairz, K. and F. Klein (1997). “mre11S— a yeast mutation that blocks doublestrand-break processing and permits nonhomologous synapsis in meiosis.” Genes Dev 11: 2272–2290.PubMedCrossRefGoogle Scholar
  61. Oakberg, E. F. (1956). “ A description of spermatogenesis in the mouse and its use in analysis of the cycle of the seminiferous epithelium.” Am J Anat 99: 507–516.PubMedCrossRefGoogle Scholar
  62. Oakberg, E. F. (1957). “Duration of spermatogenesis in the mouse.” Nature 180: 1137–1138.PubMedCrossRefGoogle Scholar
  63. Ohta, K., A. Nicolas, et al. (1998). “Mutations in the MREI 1, 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.PubMedCrossRefGoogle Scholar
  64. Painter, R. B. (1981). “Radioresistant DNA synthesis: an intrinsic feature of ataxia telangiectasia.” Mutat Res 84: 183–190.PubMedCrossRefGoogle Scholar
  65. Painter, R. B. (1993). Radiobiology of ataxia-telangiectasia. Ataxia-telangiec- tasia. R. A. Gatti and R. B. Painter. Heidelberg, Springer-Verlag: 257–268.Google Scholar
  66. Patel, K. J., V. P. Yu, et al. (1998). “Involvement of Brca2 in DNA repair.” Mol Cell 1: 347–357.PubMedCrossRefGoogle Scholar
  67. Paull, T. T. and M. Gellert (1998). “The 3’ to 5’ exonuclease activity of Mre11 facilitates repair of DNA double-strand breaks.” Mol Cell 1: 969–979.PubMedCrossRefGoogle Scholar
  68. Paull, T. T. and M. Gellert (1999). “Nbsl potentiates ATP-driven DNA unwinding and endonuclease cleavage by the Mrel l/Rad50 complex.” Genes Dev 13: 1276–1288.PubMedCrossRefGoogle Scholar
  69. Pittman, D. L., J. Cobb, et al. (1998). “Meiotic prophase arrest with failure of chromosome synapsis in mice deficient for Dmcl, a germline-specific RecA homolog.” Mol Cell 1: 697–705.PubMedCrossRefGoogle Scholar
  70. Plug, A. W., A. H. F. M. Peters, et al. (1997). “ATM and RPA in meiotic chromosome synapsis and recombination.” Nat Genet 17: 457–461.PubMedCrossRefGoogle Scholar
  71. Plug, A. W., A. H. F. M. Peters, et al. (1998). “Changes in protein composition of meiotic nodules during mammalian meiosis.” J Cell Sci 111: 413–423.PubMedGoogle Scholar
  72. Plug, A. W., J. Xu, et al. (1996). “Presynaptic association of RAD51 protein with selected sites in meiotic chromatin.” Proc Natl Acad Sci USA 93: 5920–5924.PubMedCrossRefGoogle Scholar
  73. Radding, C. M. (1991). “Helical interactions in homologous pairing and strand exchange driven by RecA protein. ” J Biol Chem 266: 5355–5358.PubMedGoogle Scholar
  74. Rattray, A. J., C. B. McGill, (2001). “Fidelity of mitotic double-strand break repair in Saccharomyces cerevisiae: a role for SAE2/COM1.” Genetics 158: 109–122.PubMedGoogle Scholar
  75. Raymond, W. E. and N. Kleckner (1993). “RAD50 protein of S. cerevisiae exhibits ATP-dependent DNA binding.” Nucleic Acids Res 21: 3851–3856.PubMedCrossRefGoogle Scholar
  76. Robu, M. E., R. B. Inman, et al. (2001). “RecA protein promotes the regression of stalled forks in vitro.” Proc Natl Acad Sci USA 98: 8211–8218.CrossRefGoogle Scholar
  77. Roeder, G. S. (1990). “Chromosome synapsis and genetic recombination.” Trends Genet 6: 385–389.PubMedCrossRefGoogle Scholar
  78. Roeder, G. S. (1997). “Meiotic chromosomes: it takes two to tango.” Genes Dev 11: 2600–2621.PubMedCrossRefGoogle Scholar
  79. Scully, R., J. Chen, et al. (1997). “Association of BRCA1 with RAD51 in mitotic and meiotic cells.” Cell 88: 265–275.PubMedCrossRefGoogle Scholar
  80. Sharan, S. K., M. Morimatsu, et al. (1997). “Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2.” Nature 368: 804–810.CrossRefGoogle Scholar
  81. Shen, S. X., Z. Weaver, et al. (1998). “ A targeted disruption of the murine Brcal gene causes gamma-irradiation hypersensitivity and genetic instability.” Oncogene 17: 3115–3124.PubMedCrossRefGoogle Scholar
  82. Shiloh, Y. (1995). “Ataxia-Telangiectasia: Closer to unraveling the mystery.” Eur J Hum Genet 3: 116–138.PubMedGoogle Scholar
  83. Shiloh, Y. (2001). “ATM and ATR: network in cellular responses to DNA damage.” Curr Opin Genet Dey 11: 71–77.CrossRefGoogle Scholar
  84. Signon, L., A. Malkova, et al. (2001). “Genetic requirements for RAD51- and Rad54-independent break-induced replication repair of a chromosomal double-strand break.” Mol Cell Biol 21: 2048–2056.PubMedCrossRefGoogle Scholar
  85. Stewart, G. S., R. S. Maser, et al. (1999). “The DNA double-strand break repair gene hMrel 1 is mutated in individuals with an ataxia-telangiectasialike disorder.” Cell 99: 577–587.PubMedCrossRefGoogle Scholar
  86. Stillman, B. (1999). “Cell cycle control of DNA replication.” Science 274: 1659–1664.CrossRefGoogle Scholar
  87. Sullivan, K. E., E. Veksler, et al. (1997). “Cell cycle checkpoints and DNA repair in Nijmegen breakage syndrome.” Clin Immunol Immunopathol 82: 43–48.PubMedCrossRefGoogle Scholar
  88. Szostak, J. W., T. L. Orr-Weaver, et al. (1983). “The double-strand-break repair model for recombination.” Cell 33: 25–35.PubMedCrossRefGoogle Scholar
  89. Tibbetts, R. S., D. Cortez, et al. (2000). “Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress.” Genes Dey 14: 2989–3002.CrossRefGoogle Scholar
  90. Trujillo, K. M., S. S. F. Yuan, et al. (1998). “Nuclease activities in a complex of human recombination and DNA repair factors RAD50, MRE11, and p95.” JBiol Chem 273: 21447–21450.CrossRefGoogle Scholar
  91. Tsubouchi, H. and H. Ogawa (1998). “A novel mrell mutation that impairs processing of double-strand breaks of DNA during both mitosis and meiosis.” Mol Cell Biol 18: 260–268.PubMedGoogle Scholar
  92. Tsuzuki, T., Y. Fujii, et al. (1996). “Targeted disruption of the Rad51 gene leads to lethality in embryonic mice.” Proc Natl Acad Sci USA 93: 6236–6240.PubMedCrossRefGoogle Scholar
  93. Umezu, K., N. Sugawara, et al. (1998). “Genetic analysis of yeast RPAI re- veals its multiple functions in DNA metabolism.” Genetics 148: 989–1005.PubMedGoogle Scholar
  94. Varon, R., C. Vissinga, et al. (1998). “Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome.” Cell 93: 467–476.PubMedCrossRefGoogle Scholar
  95. Walpita, D., A. W. Plug, et al. (1999). “Bloom’s syndrome protein (BLM) co-localizes with RPA in meiotic prophase nuclei of mammalian spermatocytes.” Proc Natl Acad Sci USA 96: 5622–5627.PubMedCrossRefGoogle Scholar
  96. Walter, J. and J. Newport (2000). “Initiation of eukaryotic DNA replication: origin unwinding and sequential chromatin association of Cdc45, RPA, and DNA polymerase a.” Mol Cell 5: 617–627.PubMedCrossRefGoogle Scholar
  97. Weiner, B. M. and N. Kleckner (1994). “Chromosome pairing via multiple interstitial interactions before and during meiosis in yeast.” Cell 77: 977–991.PubMedCrossRefGoogle Scholar
  98. Weinert, T. (1997). “A DNA damage checkpoint meets the cell cycle engine.” Science 277: 1450–1451.PubMedCrossRefGoogle Scholar
  99. Weinert, T. and D. Lydall (1993). “Cell cycle checkpoints, genetic instability and cancer.” Cancer Biol 4: 129–140.Google Scholar
  100. Westphal, C. H. (1997). “ATM displays its many talents.” Current Biol 7: 789–792.CrossRefGoogle Scholar
  101. Wu, X., V. Ranganathan, et al. (2000). “ATM phosphorylation of Nijmegen breakage syndrome protein is required in a DNA damage response.” Nature 405: 477–482.PubMedCrossRefGoogle Scholar
  102. Xiao, Y. H. and D. T. Weaver (1997). “Conditional gene targeted deletion by Cre recombinase demonstrates the requirement for the double strand break repair gene Mrel l protein in murine embryonic stem cells.” Nucl Acid Res 25: 2985–2991.CrossRefGoogle Scholar
  103. Xu, Y., T. Ashley, et al. (1996). “Targeted disruption of ATM leads to growth retardation, chromosomal fragmentation during meiosis, immune defects, and thymic lymphoma.” Genes Dev 10: 2411–2422.PubMedCrossRefGoogle Scholar
  104. Yoshida, K., G. Kondoh, et al. (1998). “The mouse RecA-like gene DMC1 is required for homologous chromosome synapsis during meiosis.” Mol Cell 1: 707–718.PubMedCrossRefGoogle Scholar
  105. Zhu, J., S. Petersen, et al. (2001). “Targeted disruption of the Nijmegen breakage syndrome gene NSB I leads to early embryonic lethality in mice.” Curr Biol 11: 105–109.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2002

Authors and Affiliations

  • T. Ashley

There are no affiliations available

Personalised recommendations