基因组不稳定性
DNA损伤
雷达51
聚ADP核糖聚合酶
生物
细胞生物学
解旋酶
DNA修复
核糖核酸酶P
DNA
DNA复制
聚合酶
复制蛋白A
内生
分子生物学
遗传学
核糖核酸
DNA结合蛋白
生物化学
基因
转录因子
作者
Wen-Ling Lin,Jung-Kuei Chen,Xiaoyan Wen,He Wang,Geovanny A. Zarceno,Yutian Chen,Shi Chen,Tanya T. Paull,Hung‐wen Liu
出处
期刊:Cell Reports
[Elsevier]
日期:2022-07-01
卷期号:40 (3): 111089-111089
被引量:21
标识
DOI:10.1016/j.celrep.2022.111089
摘要
R loops occur frequently in genomes and contribute to fundamental biological processes at multiple levels. Consequently, understanding the molecular and cellular biology of R loops has become an emerging area of research. Here, it is shown that poly(ADP-ribose) polymerase-1 (PARP-1) can mediate the association of DDX18, a putative RNA helicase, with R loops thereby modulating R-loop homeostasis in endogenous R-loop-prone and DNA lesion regions. DDX18 depletion results in aberrant endogenous R-loop accumulation, which leads to DNA-replication defects. In addition, DDX18 depletion renders cells more sensitive to DNA-damaging agents and reduces RPA32 and RAD51 foci formation in response to irradiation. Notably, DDX18 depletion leads to γH2AX accumulation and genome instability, and RNase H1 overexpression rescues all the DNA-repair defects caused by DDX18 depletion. Taken together, these studies uncover a function of DDX18 in R-loop-mediated events and suggest a role for PARP-1 in mediating the binding of specific DDX-family proteins with R loops in cells.
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