Lamin B1 sequesters 53BP1 to control its recruitment to DNA damage.

Lamin B1 sequesters 53BP1 to control its recruitment to DNA damage.
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DOI:
10.1126/sciadv.abb3799
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发表时间:
2021-08
期刊:
影响因子:
13.6
通讯作者:
Bertrand P
Bertrand P
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Etourneaud L;Moussa A;Rass E;Genet D;Willaume S;Chabance-Okumura C;Wanschoor P;Picotto J;Thézé B;Dépagne J;Veaute X;Dizet E;Busso D;Barascu A;Irbah L;Kortulewski T;Campalans A;Le Chalony C;Zinn-Justin S;Scully R;Pennarun G;Bertrand P

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Lamin B1 控制 53BP1 招募至 DNA 损伤。双链断裂(DSB)是有害的损伤,也是基因组不稳定的主要原因。研究表明核膜和 DNA 损伤反应之间存在联系。在这里,我们发现核纤层蛋白 B1(核膜的主要成分)直接与 53BP1 蛋白相互作用,而 53BP1 蛋白在 DSB 修复中发挥着关键作用。 DNA 损伤后,这种相互作用就会解离。 Lamin B1 过度表达会阻碍 53BP1 募集到 DNA 损伤位点,并导致 DNA 损伤持续存在、非同源末端连接缺陷以及对 DSB 的敏感性增加。核纤层蛋白 B1 和 53BP1 之间相互作用域的鉴定使我们能够证明,核纤层蛋白 B1 过表达时 53BP1 招募的缺陷和 DSB 持续存在是由于核纤层蛋白 B1 对 53BP1 的隔离所致。这项研究强调核纤层蛋白 B1 作为控制损伤后 53BP1 募集到 DNA 损伤位点的因素。
Lamin B1 controls 53BP1 recruitment to DNA damage. Double-strand breaks (DSBs) are harmful lesions and a major cause of genome instability. Studies have suggested a link between the nuclear envelope and the DNA damage response. Here, we show that lamin B1, a major component of the nuclear envelope, interacts directly with 53BP1 protein, which plays a pivotal role in the DSB repair. This interaction is dissociated after DNA damage. Lamin B1 overexpression impedes 53BP1 recruitment to DNA damage sites and leads to a persistence of DNA damage, a defect in nonhomologous end joining and an increased sensitivity to DSBs. The identification of interactions domains between lamin B1 and 53BP1 allows us to demonstrate that the defect of 53BP1 recruitment and the DSB persistence upon lamin B1 overexpression are due to sequestration of 53BP1 by lamin B1. This study highlights lamin B1 as a factor controlling the recruitment of 53BP1 to DNA damage sites upon injury.
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