Regulation of 53BP1 protein stability by RNF8 and RNF168 is important for efficient DNA double-strand break repair.
Regulation of 53BP1 protein stability by RNF8 and RNF168 is important for efficient DNA double-strand break repair.
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DOI：
10.1371/journal.pone.0110522
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Mondal N
中科院分区：
文献类型：
--
作者：
Hu Y;Wang C;Huang K;Xia F;Parvin JD;Mondal N
53 BP 1调节DNA双链断裂（DSB）修复。在特异性DSB修复途径的功能测定中，我们发现53 BP 1在保守的非同源末端连接（C-NHEJ）途径中是重要的，并且这种活性依赖于RNF 8和RNF 168。我们观察到，53 BP 1蛋白在细胞核中弥漫丰富，并且在电离辐射下，53 BP 1除了在DNA损伤位点之外到处都被降解。RNF 8或RNF 168的耗尽阻断了弥散定位的核53 BP 1的降解，并且不形成电离辐射诱导的灶（IRIF）。此外，当53 BP 1降解被抑制时，53 BP 1的一个子集被结合到DNA损伤位点，但大量未结合的53 BP 1保留在核质中，并且其下游效应物RIF 1在DSB的定位被取消。我们的数据表明，一种新的机制，响应DSB电离辐射后，53 BP 1被分为两个群体，确保功能DSB修复：损伤位点结合的53 BP 1，其结合信号是由RNF 8和RNF 168产生的;和未结合的散装53 BP 1，其随后的降解由RNF 8和RNF 168调节。
53BP1 regulates DNA double-strand break (DSB) repair. In functional assays for specific DSB repair pathways, we found that 53BP1 was important in the conservative non-homologous end-joining (C-NHEJ) pathway, and this activity was dependent upon RNF8 and RNF168. We observed that 53BP1 protein was diffusely abundant in nuclei, and upon ionizing radiation, 53BP1 was everywhere degraded except at DNA damage sites. Depletion of RNF8 or RNF168 blocked the degradation of the diffusely localized nuclear 53BP1, and ionizing radiation induced foci (IRIF) did not form. Furthermore, when 53BP1 degradation was inhibited, a subset of 53BP1 was bound to DNA damage sites but bulk, unbound 53BP1 remained in the nucleoplasm, and localization of its downstream effector RIF1 at DSBs was abolished. Our data suggest a novel mechanism for responding to DSB that upon ionizing radiation, 53BP1 was divided into two populations, ensuring functional DSB repair: damage site-bound 53BP1 whose binding signal is known to be generated by RNF8 and RNF168; and unbound bulk 53BP1 whose ensuing degradation is regulated by RNF8 and RNF168.
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影响因子：
16
作者：
Bothmer A;Robbiani DF;Di Virgilio M;Bunting SF;Klein IA;Feldhahn N;Barlow J;Chen HT;Bosque D;Callen E;Nussenzweig A;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
4.8
作者：
Hu, Yiheng;Parvin, Jeffrey D.
通讯作者：
Parvin, Jeffrey D.
由 53BP1-RIF1 和 BRCA1-CtIP 组成的细胞周期依赖性调节回路控制 DNA 修复途径的选择。
影响因子：
16
作者：
Escribano-Diaz, Cristina;Orthwein, Alexandre;Durocher, Daniel
通讯作者：
Durocher, Daniel
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
5.3
作者：
FISHMANLOBELL, J;RUDIN, N;HABER, JE
通讯作者：
HABER, JE