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Title: Mutations that affect meiosis in male mice influence the dynamics of the mid-preleptotene and bouquet stages

Journal Article · · Experimental Cell Research
 [1];  [2];  [3];  [2];  [4];  [5];  [6];  [3];  [7];  [8];  [9];  [10];  [11];  [3];  [2];  [12]
  1. Max-Planck-Inst. for Molecular Genetics, Ihnestr. 73, D-14195 Berlin (Germany)
  2. Genetics and Biochemistry Branch, NIDDK, National Inst. of Health, Bethesda, MD 20892 (United States)
  3. Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States)
  4. GSF-Forschungszentrum fuer Umwelt und Gesundheit GmbH, Institut fuer Molekulare Strahlenbiologie, Biostatistics, Neuherberg, D-80937 Munich (Germany)
  5. Department of Mol. Cell Biol., Res. Inst. for Microbial Diseases, Osaka University, Osaka 565-0871 (Japan)
  6. Department of Radiation Oncology, Washington Univ. School of Medicine, St. Louis, MO 63108 (United States)
  7. Gene Resp. Section, Center for Cancer Research, NCI, Bethesda, MD (United States)
  8. University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 (United States)
  9. Department of Reprod. and Dev., Erasmus MC, 3000 CA Rotterdam (Netherlands)
  10. Center for Vertebrate Genomics, Dept. of Biomed. Sci., College of Vet. Med., Cornell University, Ithaca, NY 14853 (United States)
  11. Laboratory for Cell Biology and Genetics, Rockefeller University, New York, NY 10021 (United States)
  12. Max-Planck-Inst. for Molecular Genetics, Ihnestr. 73, D-14195 Berlin (Germany) and Bundeswehr Institute of Radiobiology, Neuherbergstr. 11, 80937 Munich (Germany)

Meiosis pairs and segregates homologous chromosomes and thereby forms haploid germ cells to compensate the genome doubling at fertilization. Homologue pairing in many eukaryotic species depends on formation of DNA double strand breaks (DSBs) during early prophase I when telomeres begin to cluster at the nuclear periphery (bouquet stage). By fluorescence in situ hybridization criteria, we observe that mid-preleptotene and bouquet stage frequencies are altered in male mice deficient for proteins required for recombination, ubiquitin conjugation and telomere length control. The generally low frequencies of mid-preleptotene spermatocytes were significantly increased in male mice lacking recombination proteins SPO11, MEI1, MLH1, KU80, ubiquitin conjugating enzyme HR6B, and in mice with only one copy of the telomere length regulator Terf1. The bouquet stage was significantly enriched in Atm {sup -/-}, Spo11 {sup -/-}, Mei1 {sup m1Jcs/m1Jcs}, Mlh1 {sup -/-}, Terf1 {sup +/-} and Hr6b {sup -/-} spermatogenesis, but not in mice lacking recombination proteins DMC1 and HOP2, the non-homologous end-joining DNA repair factor KU80 and the ATM downstream effector GADD45a. Mice defective in spermiogenesis (Tnp1 {sup -/-}, Gmcl1 {sup -/-}, Asm {sup -/-}) showed wild-type mid-preleptotene and bouquet frequencies. A low frequency of bouquet spermatocytes in Spo11 {sup -/-} Atm {sup -/-} spermatogenesis suggests that DSBs contribute to the Atm {sup -/-}-correlated bouquet stage exit defect. Insignificant changes of bouquet frequencies in mice with defects in early stages of DSB repair (Dmc1 {sup -/-}, Hop2 {sup -/-}) suggest that there is an ATM-specific influence on bouquet stage duration. Altogether, it appears that several pathways influence telomere dynamics in mammalian meiosis.

OSTI ID:
20858054
Journal Information:
Experimental Cell Research, Vol. 312, Issue 19; Other Information: DOI: 10.1016/j.yexcr.2006.07.019; PII: S0014-4827(06)00299-0; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
Country of Publication:
United States
Language:
English