生物
同源重组
核糖核酸
核酸酶
DNA
非同源性末端接合
DNA修复
分子生物学
聚合酶
细胞生物学
遗传学
基因
作者
Sijie Liu,Hua Yu,Jingna Wang,Lingyan Li,Junjie Yuan,Bo Zhang,Ziyang Wang,Jianguo Ji,Daochun Kong
出处
期刊:Cell
[Elsevier]
日期:2021-03-01
卷期号:184 (5): 1314-1329.e10
被引量:102
标识
DOI:10.1016/j.cell.2021.01.048
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI