The Sm core components of small nuclear ribonucleoproteins promote homologous recombination repair.
The Sm core components of small nuclear ribonucleoproteins promote homologous recombination repair.
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DOI：
10.1016/j.dnarep.2021.103244
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发表时间：
2021-12
期刊：
影响因子：
3.8
通讯作者：
Peng A
中科院分区：
文献类型：
--
作者：
Li Y;Kardell MB;Wang F;Wang L;Zhu S;Bessho T;Peng A
DNA双链断裂(DSB)对细胞危害很大，主要通过非同源末端连接(NHEJ)和同源重组(HR)修复。利用模拟DSB的DNA模板，我们的蛋白质组学研究确定了一组小核核糖核蛋白(SnRNPs)的Sm核心蛋白是潜在的DSB相关蛋白。我们进一步证实，这些Sm蛋白被招募到激光诱导的DNA损伤部位，并与已建立的DNA损伤修复因子共定位。Sm-D3或Sm-B的缺失可诱导γ-H_2AX的积聚，并降低HR的修复效率，但不影响HR的修复效率。此外，Sm-D3的阻断降低了HR因子的蛋白水平，尤其是RAD51和CHK1，但不改变NHEJ中涉及的修复因子的表达。从机制上讲，Sm-D3蛋白结合RAD51，抑制RAD51泛素化，并介导RAD51的稳定；Sm-D3缺失尤其影响受损染色质上RAD51和CHK1的水平。因此，我们的研究通过一种新的机制表征了Sm蛋白在HR修复中的作用，这种新机制不同于它们在RNA加工和基因调控中的传统功能，但与它们直接募集到DNA损伤部位和与修复因子相关联。
DNA Double strand breaks (DSBs) are highly hazardous to the cell, and are repaired predominantly via non-homologous end joining (NHEJ) and homologous recombination (HR). Using DSB-mimicking DNA templates, our proteomic studies identified a group of Sm core proteins of small nuclear ribonucleoproteins (snRNPs) as potential DSB-associated proteins. We further confirmed that these Sm proteins were recruited to laser-induced DNA damage sites, and co-localized with established DNA damage repair factors. Depletion of Sm-D3 or Sm-B induced accumulation of γ-H2AX, and impaired the repair efficiency of HR, but not NHEJ. Furthermore, disruption of Sm-D3 reduced the protein level of HR factors, especially RAD51 and CHK1, but caused no change in the expression of repair factors involved in NHEJ. Mechanistically, Sm-D3 proteins bound RAD51, suppressed the ubiquitination of RAD51, and mediated the stabilization of RAD51; Sm-D3 depletion particularly impacted the level of RAD51 and CHK1 on damaged chromatin. As such, our studies characterized a role of Sm proteins in HR repair, via a new mechanism that is distinct from their conventional functions in RNA processing and gene regulation, but consistent with their direct recruitment to DNA damage sites and association with repair factors.
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影响因子：
8
作者：
Bahassi, E. M.;Ovesen, J. L.;Stambrook, P. J.
通讯作者：
Stambrook, P. J.
影响因子：
3.2
作者：
Li, Yuyang;Li, Jia;Liu, Weiwei
通讯作者：
Liu, Weiwei
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：
Ciccia A;Elledge SJ
通讯作者：
Elledge SJ
影响因子：
10.3
作者：
Hoppe, Michal M.;Sundar, Raghav;Jeyasekharan, Anand D.
通讯作者：
Jeyasekharan, Anand D.