Rad51 replication fork recruitment is required for DNA damage tolerance
Rad51 replication fork recruitment is required for DNA damage tolerance
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DOI：
10.1038/emboj.2013.73
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发表时间：
2013-05-02
期刊：
影响因子：
11.4
通讯作者：
Prado, Felix
中科院分区：
文献类型：
--
作者：
Gonzalez-Prieto, Roman;Munoz-Cabello, Ana M.;Prado, Felix
同源重组是基因组完整性的重要组成部分。重组蛋白参与耐受干扰DNA复制的DNA损伤，但当它们没有得到适当调节时，也会产生有毒的重组中间体和遗传不稳定。在这里，我们研究了重组蛋白Rad51和Rad52在复制叉和复制性DNA损伤中的作用。我们发现Rad52将Rad51装载到未受干扰的复制叉上，在那里它们通过非修复功能促进烷基化DNA的复制。在DNA复制过程中，Rad52和Rad51在染色质上的招募是修复非dsb DNA损伤（可能是烷基化DNA复制过程中产生的单链DNA缺口）的先决条件。我们还表明，这些病变的修复需要CDK1，并且不与分叉耦合，而是由复制检查点限制为G2/M。我们提出了一种新的HR情景，即Rad52和Rad51被招募到分叉上，通过不同的细胞周期调节的复制和修复功能来促进DNA损伤耐受性。
Homologous recombination (HR) is essential for genome integrity. Recombination proteins participate in tolerating DNA lesions that interfere with DNA replication, but can also generate toxic recombination intermediates and genetic instability when they are not properly regulated. Here, we have studied the role of the recombination proteins Rad51 and Rad52 at replication forks and replicative DNA lesions. We show that Rad52 loads Rad51 onto unperturbed replication forks, where they facilitate replication of alkylated DNA by non-repair functions. The recruitment of Rad52 and Rad51 to chromatin during DNA replication is a prerequisite for the repair of the non-DSB DNA lesions, presumably single-stranded DNA gaps, which are generated during the replication of alkylated DNA. We also show that the repair of these lesions requires CDK1 and is not coupled to the fork but rather restricted to G2/M by the replicative checkpoint. We propose a new scenario for HR where Rad52 and Rad51 are recruited to the fork to promote DNA damage tolerance by distinct and cell cycle-regulated replicative and repair functions.