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

Comprehensive, fine-scale dissection of homologous recombination outcomes at a hot spot in mouse meiosis.
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DOI:
10.1016/j.molcel.2010.08.017
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发表时间:
2010-09-10
期刊:
影响因子:
16
通讯作者:
Jasin M
Jasin M
中科院分区:
生物学1区
文献类型:
--
作者:
Cole F;Keeney S;Jasin M

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在哺乳动物减数分裂中,只有一小部分程序性DNA双链断裂作为同源物间交换(CO)被修复。为了分析减数分裂重组的另一种产物,同源物间非交换(NCO),我们在来自近交系小鼠品系的F1杂交种中强烈活跃的小鼠热点处进行了重组事件的高分辨率映射。我们提供的直接证据表明,绝大多数修复事件是同源物间的NCO,与频繁的同源物间相互作用促进准确的染色体配对的模型一致。士官在热点中心达到顶峰,但也广泛分布在各地。在一些杂交菌株中,热点内的局部区域对CO高度难治,并且显示出NCO中相邻多态性的共转换频率升高,从而提高了双链缺口修复的可能性。在一个混合动力系统中观察到传输失真,NCO提供了显着的贡献。因此,NCO重组事件在哺乳动物减数分裂和基因组进化中起着重要作用。
In mammalian meiosis, only a small fraction of programmed DNA double-strand breaks are repaired as inter-homolog crossovers (COs). To analyze another product of meiotic recombination, inter-homolog noncrossovers (NCOs), we performed high-resolution mapping of recombination events at an intensely active mouse hotspot in F1 hybrids derived from inbred mouse strains. We provide direct evidence that the vast majority of repair events are inter-homolog NCOs, consistent with models in which frequent inter-homolog interactions promote accurate chromosome pairing. NCOs peaked at the center of the hotspot, but were also broadly distributed throughout. In some hybrid strains, localized zones within the hotspot were highly refractory to COs and showed elevated frequency of co-conversion 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.
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