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Meiotic recombination mirrors patterns of germline replication in mice and humans
Cell ( IF 64.5 ) Pub Date : 2021-07-13 , DOI: 10.1016/j.cell.2021.06.025
Florencia Pratto 1 , Kevin Brick 1 , Gang Cheng 1 , Kwan-Wood Gabriel Lam 1 , Jeffrey M Cloutier 1 , Daisy Dahiya 1 , Stephen R Wellard 2 , Philip W Jordan 2 , R Daniel Camerini-Otero 1
Affiliation  

Genetic recombination generates novel trait combinations, and understanding how recombination is distributed across the genome is key to modern genetics. The PRDM9 protein defines recombination hotspots; however, megabase-scale recombination patterning is independent of PRDM9. The single round of DNA replication, which precedes recombination in meiosis, may establish these patterns; therefore, we devised an approach to study meiotic replication that includes robust and sensitive mapping of replication origins. We find that meiotic DNA replication is distinct; reduced origin firing slows replication in meiosis, and a distinctive replication pattern in human males underlies the subtelomeric increase in recombination. We detected a robust correlation between replication and both contemporary and historical recombination and found that replication origin density coupled with chromosome size determines the recombination potential of individual chromosomes. Our findings and methods have implications for understanding the mechanisms underlying DNA replication, genetic recombination, and the landscape of mammalian germline variation.



中文翻译:

减数分裂重组反映了小鼠和​​人类种系复制的模式

基因重组产生新的性状组合,了解重组如何在基因组中分布是现代遗传学的关键。PRDM9 蛋白定义了重组热点;然而,兆碱基规模的重组模式独立于 PRDM9。减数分裂重组之前的单轮 DNA 复制可能会建立这些模式。因此,我们设计了一种研究减数分裂复制的方法,其中包括复制起点的稳健和敏感映射。我们发现减数分裂 DNA 复制是不同的;减少的起源激发减慢了减数分裂中的复制,而人类男性中独特的复制模式是亚端粒重组增加的基础。我们检测到复制与当代和历史重组之间存在强大的相关性,并发现复制起点密度与染色体大小相结合决定了单个染色体的重组潜力。我们的发现和方法对理解 DNA 复制、基因重组和哺乳动物生殖系变异的潜在机制具有重要意义。

更新日期:2021-08-05
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