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Comprehensive, fine-scale dissection of homologous recombination outcomes at a hot spot in mouse meiosis.

ABSTRACT: In mammalian meiosis, only a small fraction of programmed DNA double-strand breaks are repaired as interhomolog crossovers (COs). To analyze another product of meiotic recombination, interhomolog noncrossovers (NCOs), we performed high-resolution mapping of recombination events at an intensely active mouse hot spot in F1 hybrids derived from inbred mouse strains. We provide direct evidence that the vast majority of repair events are interhomolog NCOs, consistent with models in which frequent interhomolog interactions promote accurate chromosome pairing. NCOs peaked at the center of the hot spot but were also broadly distributed throughout. In some hybrid strains, localized zones within the hot spot were highly refractory to COs and showed elevated frequency of coconversion of adjacent polymorphisms in NCOs, raising the possibility of double-strand gap repair. Transmission distortion was observed in one hybrid, with NCOs providing a significant contribution. Thus, NCO recombination events play a substantial role in mammalian meiosis and genome evolution.

SUBMITTER: Cole F

PROVIDER: S-EPMC3196603 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Comprehensive, fine-scale dissection of homologous recombination outcomes at a hot spot in mouse meiosis.

Cole Francesca F Keeney Scott S Jasin Maria M

Molecular cell 20100901 5

In mammalian meiosis, only a small fraction of programmed DNA double-strand breaks are repaired as interhomolog crossovers (COs). To analyze another product of meiotic recombination, interhomolog noncrossovers (NCOs), we performed high-resolution mapping of recombination events at an intensely active mouse hot spot in F1 hybrids derived from inbred mouse strains. We provide direct evidence that the vast majority of repair events are interhomolog NCOs, consistent with models in which frequent int ...[more]

PMID: 20832722

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Project description:The intimate synapsis of homologous chromosome pairs (homologs) by synaptonemal complexes (SCs) is an essential feature of meiosis. In many organisms, synapsis and homologous recombination are interdependent: recombination promotes SC formation and SCs are required for crossing-over. Moreover, several studies indicate that initiation of SC assembly occurs at sites where crossovers will subsequently form. However, recent analyses in budding yeast and fruit fly imply a special role for centromeres in the initiation of SC formation. In addition, in budding yeast, persistent SC-dependent centromere-association facilitates the disjunction of chromosomes that have failed to become connected by crossovers. Here, we examine the interplay between SCs, recombination, and centromeres in a mammal. In mouse spermatocytes, centromeres do not serve as SC initiation sites and are invariably the last regions to synapse. However, centromeres are refractory to de-synapsis during diplonema and remain associated by short SC fragments. Since SC-dependent centromere association is lost before diakinesis, a direct role in homolog segregation seems unlikely. However, post-SC disassembly, we find evidence of inter-centromeric connections that could play a more direct role in promoting homolog biorientation and disjunction. A second class of persistent SC fragments is shown to be crossover-dependent. Super-resolution structured-illumination microscopy (SIM) reveals that these structures initially connect separate homolog axes and progressively diminish as chiasmata form. Thus, DNA crossing-over (which occurs during pachynema) and axis remodeling appear to be temporally distinct aspects of chiasma formation. SIM analysis of the synapsis and crossover-defective mutant Sycp1?/? implies that SCs prevent unregulated fusion of homolog axes. We propose that SC fragments retained during diplonema stabilize nascent bivalents and help orchestrate local chromosome reorganization that promotes centromere and chiasma function.

Dataset Information

Comprehensive, fine-scale dissection of homologous recombination outcomes at a hot spot in mouse meiosis.

Publications

Comprehensive, fine-scale dissection of homologous recombination outcomes at a hot spot in mouse meiosis.

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