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Mutations that affect meiosis in male mice influence the dynamics of the mid-preleptotene and bouquet stages. Exp Cell Res

Max-Planck-Inst. for Molecular Genetics, Ihnestr. 73, D-14195 Berlin, Germany.
Experimental Cell Research (Impact Factor: 3.25). 12/2006; 312(19):3768-81. DOI: 10.1016/j.yexcr.2006.07.019
Source: PubMed

ABSTRACT

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(-/-), Spo11(-/-), Mei1(m1Jcs/m1Jcs), Mlh1(-/-), Terf1(+/-) and Hr6b(-/-) 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(-/-), Gmcl1(-/-), Asm(-/-)) showed wild-type mid-preleptotene and bouquet frequencies. A low frequency of bouquet spermatocytes in Spo11(-/-)Atm(-/-) spermatogenesis suggests that DSBs contribute to the Atm(-/-)-correlated bouquet stage exit defect. Insignificant changes of bouquet frequencies in mice with defects in early stages of DSB repair (Dmc1(-/-), Hop2(-/-)) suggest that there is an ATM-specific influence on bouquet stage duration. Altogether, it appears that several pathways influence telomere dynamics in mammalian meiosis.

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    • "Both SYCP3 and γ-H2AX had a distribution similar to that of leptotene-zygotene spermatocytes, except that the staining was much more intense (compare Bnc2 −/− spermatocytes in Fig. 7M,N with normal leptotene-zygotene spermatocytes indicated by the arrowhead in Fig. 7I). We presumed that these cells were abnormal spermatocytes blocked in leptotene-zygotene (Liebe et al., 2006; Mahadevaiah et al., 2001). In other tubules, the cells in the luminal region showed filamentous SYCP3 and XY bodies typical of pachytene spermatocytes (Fig. 7N,O). "
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    • "Because deletion of Spo11 from Atm knockout suppresses bouquet arrest, the ATM kinase-mediated DNA damage response, which is associated with SPO11-dependent DSBs, might be required for the exit from the bouquet stage (Pandita et al. 1999; Fernandez-Capetillo et al. 2003; Liebe et al. 2006). Also, in Sordaria Spo11 mutants, the bouquet stage persists longer than in wild-type cells. "
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