Regulation of Rad52-dependent replication fork recovery through serine ADP-ribosylation of PolD3.
Regulation of Rad52-dependent replication fork recovery through serine ADP-ribosylation of PolD3.
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DOI：
10.1038/s41467-023-40071-w
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发表时间：
2023-07-18
影响因子：
16.6
通讯作者：
Lakin, Nicholas D.
中科院分区：
文献类型：
--
作者：
Richards, Frederick;Llorca-Cardenosa, Marta J.;Langton, Jamie;Buch-Larsen, Sara C.;Shamkhi, Noor F.;Sharma, Abhishek Bharadwaj;Nielsen, Michael L.;Lakin, Nicholas D.
虽然聚（ADP-核糖）-聚合酶（PARP）是基因组稳定性的关键调节因子，但位点特异性ADP-核糖基化如何调节DNA修复尚不清楚。在这里，我们描述了PARP 1和PARP 2在调节Rad 52依赖性复制叉修复中的新作用，以在同源重组功能障碍时维持细胞活力，抑制复制相关的DNA损伤，并维持基因组稳定性。从机制上讲，Mre 11和ATM是诱导PARP活性所必需的，以响应复制应激，进而通过在停滞/受损的复制叉处组装Rad 52来促进断裂诱导复制（BIR）。此外，通过绘制复制应激诱导的ADP-核糖基化位点，我们确定PolD 3是PARP 1/PARP 2的靶标，并且其位点特异性ADP-核糖基化是BIR活性、复制叉恢复和基因组稳定性所需的。总的来说，这些数据确定了Mre 11依赖性PARP激活和位点特异性ADP核糖基化在调节BIR以维持DNA合成期间基因组完整性方面的关键作用。在这里，作者确定PARP 1通过断裂诱导的复制调节复制叉恢复来维持基因组完整性。从机制上讲，这是通过MRE 11依赖性PARP 1激活和PolD 3的位点特异性ADP核糖基化来实现的。
Although Poly(ADP-ribose)-polymerases (PARPs) are key regulators of genome stability, how site-specific ADP-ribosylation regulates DNA repair is unclear. Here, we describe a novel role for PARP1 and PARP2 in regulating Rad52-dependent replication fork repair to maintain cell viability when homologous recombination is dysfunctional, suppress replication-associated DNA damage, and maintain genome stability. Mechanistically, Mre11 and ATM are required for induction of PARP activity in response to replication stress that in turn promotes break-induced replication (BIR) through assembly of Rad52 at stalled/damaged replication forks. Further, by mapping ADP-ribosylation sites induced upon replication stress, we identify that PolD3 is a target for PARP1/PARP2 and that its site-specific ADP-ribosylation is required for BIR activity, replication fork recovery and genome stability. Overall, these data identify a critical role for Mre11-dependent PARP activation and site-specific ADP-ribosylation in regulating BIR to maintain genome integrity during DNA synthesis. Here the authors identify that PARP1 maintains genome integrity by regulating replication fork recovery by break-induced replication. Mechanistically, this is achieved through MRE11-dependent PARP1 activation and site-specific ADP-ribosylation of PolD3.
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影响因子：
16.8
作者：
Berti, Matteo;Chaudhuri, Arnab Ray;Thangavel, Saravanabhavan;Gomathinayagam, Shivasankari;Kenig, Sasa;Vujanovic, Marko;Odreman, Federico;Glatter, Timo;Graziano, Simona;Mendoza-Maldonado, Ramiro;Marino, Francesca;Lucic, Bojana;Biasin, Valentina;Gstaiger, Matthias;Aebersold, Ruedi;Sidorova, Julia M.;Monnat, Raymond J., Jr.;Lopes, Massimo;Vindigni, Alessandro
通讯作者：
Vindigni, Alessandro
DOI：
10.1038/nrm.2017.53
发表时间：
2017-10
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Ray Chaudhuri A;Nussenzweig A
通讯作者：
Nussenzweig A
影响因子：
16
作者：
Dias, Mariana Paes;Tripathi, Vivek;van der Heijden, Ingrid;Cong, Ke;Manolika, Eleni-Maria;Bhin, Jinhyuk;Gogola, Ewa;Galanos, Panagiotis;Annunziato, Stefano;Lieftink, Cor;Andujar-Sanchez, Miguel;Chakrabarty, Sanjiban;Smith, Graeme C. M.;van de Ven, Marieke;Beijersbergen, Roderick L.;Bartkova, Jirina;Rottenberg, Sven;Cantor, Sharon;Bartek, Jiri;Chaudhuri, Arnab Ray;Jonkers, Jos
通讯作者：
Jonkers, Jos
影响因子：
7
作者：
Hendriks, Ivo A.;Larsen, Sara C.;Nielsen, Michael L.
通讯作者：
Nielsen, Michael L.
影响因子：
16.6
作者：
Chanut, Pauline;Britton, Sebastien;Coates, Julia;Jackson, Stephen P.;Calsou, Patrick
通讯作者：
Calsou, Patrick