RNA 聚合酶 III 对于同源重组修复 DNA 双链断裂是必需的。
RNA polymerase III is required for the repair of DNA double-strand breaks by homologous recombination.
机构信息
Peking-Tsinghua Center for Life Sciences, The National Laboratory of Protein and Plant Gene research, College of Life Sciences, Peking University, Beijing 100871, China.
Peking-Tsinghua Center for Life Sciences, The National Laboratory of Protein and Plant Gene research, College of Life Sciences, Peking University, Beijing 100871, China.
出版信息
Cell. 2021 Mar 4;184(5):1314-1329.e10. doi: 10.1016/j.cell.2021.01.048. Epub 2021 Feb 23.
End resection in homologous recombination (HR) and HR-mediated repair of DNA double-strand breaks (DSBs) removes several kilobases from 5' strands of DSBs, but 3' strands are exempted from degradation. The mechanism by which the 3' overhangs are protected has not been determined. Here, we established that the protection of 3' overhangs is achieved through the transient formation of RNA-DNA hybrids. The DNA strand in the hybrids is the 3' ssDNA overhang, while the RNA strand is newly synthesized. RNA polymerase III (RNAPIII) is responsible for synthesizing the RNA strand. Furthermore, RNAPIII is actively recruited to DSBs by the MRN complex. CtIP and MRN nuclease activity is required for initiating the RNAPIII-mediated RNA synthesis at DSBs. A reduced level of RNAPIII suppressed HR, and genetic loss > 30 bp increased at DSBs. Thus, RNAPIII is an essential HR factor, and the RNA-DNA hybrid is an essential repair intermediate for protecting the 3' overhangs in DSB repair.
同源重组 (HR) 末端切除和 HR 介导的 DNA 双链断裂 (DSB) 修复会从 DSB 的 5'链上切除几个千碱基，但 3'链不会被降解。保护 3'突出端的机制尚未确定。在这里，我们发现 3'突出端的保护是通过 RNA-DNA 杂交体的瞬时形成来实现的。杂交体中的 DNA 链是 3' ssDNA 突出端，而 RNA 链是新合成的。RNA 聚合酶 III (RNAPIII) 负责合成 RNA 链。此外，MRN 复合物可将 RNAPIII 主动募集到 DSB 处。CtIP 和 MRN 核酸酶活性对于在 DSB 处启动 RNAPIII 介导的 RNA 合成是必需的。RNAPIII 水平降低会抑制 HR，并且 DSB 处的遗传缺失 > 30bp 会增加。因此，RNAPIII 是必需的 HR 因子，而 RNA-DNA 杂交体是保护 DSB 修复中 3'突出端的必需修复中间体。
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