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


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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    • "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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    ABSTRACT: During meiosis, homologous chromosome (homolog) pairing is promoted by several layers of regulation that include dynamic chromosome movement and meiotic recombination. However, the way in which homologs recognize each other remains a fundamental issue in chromosome biology. Here, we show that homolog recognition or association initiates upon entry into meiotic prophase before axis assembly and double-strand break (DSB) formation. This homolog association develops into tight pairing only during or after axis formation. Intriguingly, the ability to recognize homologs is retained in Sun1 knockout spermatocytes, in which telomere-directed chromosome movement is abolished, and this is the case even in Spo11 knockout spermatocytes, in which DSB-dependent DNA homology search is absent. Disruption of meiosis-specific cohesin RAD21L precludes the initial association of homologs as well as the subsequent pairing in spermatocytes. These findings suggest the intriguing possibility that homolog recognition is achieved primarily by searching for homology in the chromosome architecture as defined by meiosis-specific cohesin rather than in the DNA sequence itself.
    Genes & development 03/2014; 28(6). DOI:10.1101/gad.237313.113 · 10.80 Impact Factor
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    • "In particular, crossover frequency in male mice is known to vary across different inbred strains (Koehler et al. 2002) and these differences have been exploited to map genetic loci affecting recombination rates in F 2 intercrosses (Murdoch et al. 2010; Dumont and Payseur 2011). Finally, mutations at several genes are known to lead to pathological changes in recombination (Niedzwiedz et al. 2004; Liebe et al. 2006). Traditionally recombination has been studied in large pedigrees, using small numbers of informative markers. "
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