Chromatin architecture may dictate the target site for DMC1, but not for RAD51, during homologous pairing.
Chromatin architecture may dictate the target site for DMC1, but not for RAD51, during homologous pairing.
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DOI：
10.1038/srep24228
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发表时间：
2016-04-07
影响因子：
4.6
通讯作者：
Kurumizaka H
中科院分区：
文献类型：
--
作者：
Kobayashi W;Takaku M;Machida S;Tachiwana H;Maehara K;Ohkawa Y;Kurumizaka H
在真核生物中，基因组DNA被压缩成染色质，其中组蛋白和DNA形成核小体作为基本单位。DMC1和RAD51是真核生物同源重组过程中介导同源染色体配对的重要重组酶。然而，这两种重组酶在染色质中发挥作用的方式仍然难以捉摸。在这里，我们发现，在染色质中，人类dmc1单链DNA复合物绕过与核小体的结合，并优先促进核小体缺失区域的同源配对。一致地，DMC1与无核小体的DNA或核小体缺失的DNA区域形成三元复合重组中间体。令人惊讶的是，去除组蛋白尾部不正确地增强了DMC1与核小体的结合。相反，RAD51并不特异性靶向染色质中的核小体缺失区域。这是首次证明染色质结构指定了促进DMC1同源重组反应的位点，而不是RAD51。
In eukaryotes, genomic DNA is compacted as chromatin, in which histones and DNA form the nucleosome as the basic unit. DMC1 and RAD51 are essential eukaryotic recombinases that mediate homologous chromosome pairing during homologous recombination. However, the means by which these two recombinases distinctly function in chromatin have remained elusive. Here we found that, in chromatin, the human DMC1-single-stranded DNA complex bypasses binding to the nucleosome, and preferentially promotes homologous pairing at the nucleosome-depleted regions. Consistently, DMC1 forms ternary complex recombination intermediates with the nucleosome-free DNA or the nucleosome-depleted DNA region. Surprisingly, removal of the histone tails improperly enhances the nucleosome binding by DMC1. In contrast, RAD51 does not specifically target the nucleosome-depleted region in chromatin. These are the first demonstrations that the chromatin architecture specifies the sites to promote the homologous recombination reaction by DMC1, but not by RAD51.