Comprehensive, Fine-Scale Dissection of Homologous Recombination Outcomes at a Hot Spot in Mouse Meiosis

被引:80
作者
Cole, Francesca [2 ]
Keeney, Scott [1 ,3 ]
Jasin, Maria [2 ]
机构
[1] Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, New York, NY 10065 USA
[2] Mem Sloan Kettering Canc Ctr, Dev Biol Program, New York, NY 10065 USA
[3] Mem Sloan Kettering Canc Ctr, Mol Biol Program, New York, NY 10065 USA
基金
美国国家卫生研究院;
关键词
MEIOTIC RECOMBINATION; GENE CONVERSION; BREAK REPAIR; CROSSOVER; DNA; PATHWAYS; DRIVE; SPERM; PRDM9; YEAST;
D O I
10.1016/j.molcel.2010.08.017
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:700 / 710
页数:11
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