Hed1 regulates Rad51-mediated recombination via a novel mechanism
Hed1 regulates Rad51-mediated recombination via a novel mechanism
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DOI：
10.1101/gad.1638708
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发表时间：
2008-03-15
影响因子：
10.5
通讯作者：
Sung, Patrick
中科院分区：
文献类型：
--
作者：
Busygina, Valeria;Sehorn, Michael G.;Sung, Patrick
两个RecA直系同源物Rad 51和Dmc 1介导减数分裂细胞中的同源重组。在芽殖酵母减数分裂过程中，Hed 1通过下调Rad 51活性来协调Rad 51和Dmc 1的作用。据认为，Rad 51的Hed 1依赖性衰减促进了在第一次减数分裂时正确分离染色体所必需的交换的形成。我们纯化了Hed 1以阐明其作用机制。Hed 1以高亲和力和特异性结合Rad 51。我们发现，Hed 1不会对Rad 51突触前纤维的组装产生不利影响，但它特别禁止Rad 51与Rad 54的相互作用，Rad 54是Rad 51介导的重组所不可或缺的Swi 2/Snf 2样因子。与生化结果一致，Hed 1阻止了Rad 54在体内的位点特异性DNA双链断裂的招募，但对Rad 51的招募没有影响。这些发现揭示了Hed 1的功能，重要的是，揭示了一种调节同源重组的新机制。
Two RecA orthologs, Rad51 and Dmc1, mediate homologous recombination in meiotic cells. During budding yeast meiosis, Hed1 coordinates the actions of Rad51 and Dmc1 by down-regulating Rad51 activity. It is thought that Hed1-dependent attenuation of Rad51 facilitates formation of crossovers that are necessary for the correct segregation of chromosomes at the first meiotic division. We purified Hed1 in order to elucidate its mechanism of action. Hed1 binds Rad51 with high affinity and specificity. We show that Hed1 does not adversely affect assembly of the Rad51 presynaptic filament, but it specifically prohibits interaction of Rad51 with Rad54, a Swi2/Snf2-like factor that is indispensable for Rad51-mediated recombination. In congruence with the biochemical results, Hed1 prevents the recruitment of Rad54 to a site-specific DNA double-strand break in vivo but has no effect on the recruitment of Rad51. These findings shed light on the function of Hed1 and, importantly, unveil a novel mechanism for the regulation of homologous recombination.