研究人员表示，同源重组（HR）中的末端切除和HR介导的DNA双链断裂（DSB）修复能够从DSB的5'链中去除几千个碱基，但3'链却免于降解。目前尚未发现保护3'突出端的机制。
研究人员发现，RNA-DNA杂交链的瞬时形成能够实现对3'突出端的保护。杂交链中的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，RNAPIII被MRN复合物主动地招募至DSB。CtIP和MRN核酸酶活性是启动DSB处RNAPIII介导的RNA合成所必需的。RNAPIII的水平降低可抑制HR，DSB处30 bp 以上的遗传丢失则增加。因此，RNAPIII是必不可少的HR因子，而RNA-DNA杂交链是用于保护DSB修复中3'突出端的关键修复中间体。
附：英文原文
Title: RNA polymerase III is required for the repair of DNA double-strand breaks by homologous recombination
Author: Sijie Liu, Yu Hua, Jingna Wang, Lingyan Li, Junjie Yuan, Bo Zhang, Ziyang Wang, Jianguo Ji, Daochun Kong
Issue&Volume: 2021-02-23
Abstract: End resection in homologous recombination (HR) and HR-mediated repair of DNA double-strandbreaks (DSBs) removes several kilobases from 5′ strands of DSBs, but 3′ strands areexempted from degradation. The mechanism by which the 3′ overhangs are protected hasnot been determined. Here, we established that the protection of 3′ overhangs is achievedthrough the transient formation of RNA-DNA hybrids. The DNA strand in the hybridsis the 3′ ssDNA overhang, while the RNA strand is newly synthesized. RNA polymeraseIII (RNAPIII) is responsible for synthesizing the RNA strand. Furthermore, RNAPIIIis actively recruited to DSBs by the MRN complex. CtIP and MRN nuclease activity isrequired for initiating the RNAPIII-mediated RNA synthesis at DSBs. A reduced levelof RNAPIII suppressed HR, and genetic loss > 30 bp increased at DSBs. Thus, RNAPIIIis an essential HR factor, and the RNA-DNA hybrid is an essential repair intermediatefor protecting the 3′ overhangs in DSB repair.
DOI: 10.1016/j.cell.2021.01.048
Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00091-X