PARP1 associates with R-loops to promote their resolution and genome stability.
PARP1 associates with R-loops to promote their resolution and genome stability.
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DOI：
10.1093/nar/gkad066
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发表时间：
2023-03-21
影响因子：
14.9
通讯作者：
中科院分区：
文献类型：
--
作者：
PARP1是一种DNA依赖的ADP-核糖转移酶，具有ADP-核糖化活性，由DNA断裂和非B DNA结构触发，介导其拆分。PARP1最近也被发现是R-环相关蛋白质-蛋白质相互作用网络的一个组成部分，这表明PARP1在解决这一结构方面有潜在的作用。R-环是由RNA-DNA杂交体和移位的非模板DNA链组成的三链核酸结构。R-环参与关键的生理过程，但如果长期得不到解决，也可能成为基因组不稳定的来源。在这项研究中，我们证明了PARP1在体外与R-环结合，并与细胞中R-环的形成部位结合，从而激活其ADP-核糖化活性。相反，PARP1抑制或基因枯竭会导致未分解的R-环的积累，从而促进基因组的不稳定性。我们的研究表明，PARP1是一种新型的R-环传感器，并强调PARP1是R-环相关基因组不稳定性的抑制因子。PARP1与R-环结构的结合导致其多(ADP-核糖基)结合活性。PARP1基因缺失或抑制导致R环持续存在，并触发基因组不稳定。
PARP1 is a DNA-dependent ADP-Ribose transferase with ADP-ribosylation activity that is triggered by DNA breaks and non-B DNA structures to mediate their resolution. PARP1 was also recently identified as a component of the R-loop-associated protein-protein interaction network, suggesting a potential role for PARP1 in resolving this structure. R-loops are three-stranded nucleic acid structures that consist of a RNA–DNA hybrid and a displaced non-template DNA strand. R-loops are involved in crucial physiological processes but can also be a source of genome instability if persistently unresolved. In this study, we demonstrate that PARP1 binds R-loops in vitro and associates with R-loop formation sites in cells which activates its ADP-ribosylation activity. Conversely, PARP1 inhibition or genetic depletion causes an accumulation of unresolved R-loops which promotes genomic instability. Our study reveals that PARP1 is a novel sensor for R-loops and highlights that PARP1 is a suppressor of R-loop-associated genomic instability. PARP1 association with R-loop structures induces its Poly(ADP-ribosyl)ation activity. PARP1 genetic depletion or inhibition leads to R-loop persistence and triggers genome instability.
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影响因子：
3.8
作者：
Cortez D
通讯作者：
Cortez D
影响因子：
3.7
作者：
Fekete A;Kenesi E;Hunyadi-Gulyas E;Durgo H;Berko B;Dunai ZA;Bauer PI
通讯作者：
Bauer PI
影响因子：
13.6
作者：
Chatzidoukaki O;Stratigi K;Goulielmaki E;Niotis G;Akalestou-Clocher A;Gkirtzimanaki K;Zafeiropoulos A;Altmüller J;Topalis P;Garinis GA
通讯作者：
Garinis GA
影响因子：
14.9
作者：
Al-Behadili A;Uhler JP;Berglund AK;Peter B;Doimo M;Reyes A;Wanrooij S;Zeviani M;Falkenberg M
通讯作者：
Falkenberg M
影响因子：
10.5
作者：
Duquette, ML;Handa, P;Maizels, N
通讯作者：
Maizels, N