RAD51 interconnects between DNA replication, DNA repair and immunity.
RAD51 interconnects between DNA replication, DNA repair and immunity.
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DOI：
10.1093/nar/gkx126
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发表时间：
2017-05-05
影响因子：
14.9
通讯作者：
Asaithamby A
中科院分区：
文献类型：
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作者：
Bhattacharya S;Srinivasan K;Abdisalaam S;Su F;Raj P;Dozmorov I;Mishra R;Wakeland EK;Ghose S;Mukherjee S;Asaithamby A
RAD51是一种多功能蛋白，在DNA复制和同源重组修复中起着核心作用，并且已知参与癌症的发展。我们确定了RAD51在先天免疫应答信号传导中的新作用。RAD51的缺陷导致自身DNA在细胞质中的积累，在复制应激和DNA损伤后触发STING介导的先天免疫应答。在没有RAD 51的情况下，未受保护的新复制的基因组被MRE 11的核酸外切酶活性降解，并且片段化的新生DNA在胞质溶胶中积累，启动先天免疫应答。我们的数据表明，除了在同源重组介导的DNA双链断裂修复和复制叉加工中发挥作用外，RAD51还涉及先天免疫的抑制。因此，我们的研究揭示了RAD51在启动免疫信号传导中的一个先前未被表征的作用，将其置于DNA复制，DNA修复和免疫之间新的相互联系的中心。
RAD51, a multifunctional protein, plays a central role in DNA replication and homologous recombination repair, and is known to be involved in cancer development. We identified a novel role for RAD51 in innate immune response signaling. Defects in RAD51 lead to the accumulation of self-DNA in the cytoplasm, triggering a STING-mediated innate immune response after replication stress and DNA damage. In the absence of RAD51, the unprotected newly replicated genome is degraded by the exonuclease activity of MRE11, and the fragmented nascent DNA accumulates in the cytosol, initiating an innate immune response. Our data suggest that in addition to playing roles in homologous recombination-mediated DNA double-strand break repair and replication fork processing, RAD51 is also implicated in the suppression of innate immunity. Thus, our study reveals a previously uncharacterized role of RAD51 in initiating immune signaling, placing it at the hub of new interconnections between DNA replication, DNA repair, and immunity.