TRAIP/RNF206 is required for recruitment of RAP80 to sites of DNA damage.
TRAIP/RNF206 is required for recruitment of RAP80 to sites of DNA damage.
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DOI：
10.1038/ncomms10463
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发表时间：
2016-01-19
影响因子：
16.6
通讯作者：
Kim H
中科院分区：
文献类型：
--
作者：
Soo Lee N;Jin Chung H;Kim HJ;Yun Lee S;Ji JH;Seo Y;Hun Han S;Choi M;Yun M;Lee SG;Myung K;Kim Y;Chul Kang H;Kim H
RAP80定位于DNA侮辱的部位，以增强DNA损伤反应。在这里，我们发现TRAIP/RNF206是一种新的RAP80相互作用蛋白，并发现TRAIP是RAP80转移到DNA损伤所必需的。TRAIP的耗尽会导致RAP80和功能下游伙伴，包括BRCA1，在DNA损伤处的积累受损。相反，TRAIP的积聚在RAP80缺失的细胞中是正常的，这意味着TRAIP作用于RAP80募集到DNA损伤的上游。TRAIP定位于DNA损伤部位，缺失TRAIP的细胞呈现典型的DNA损伤反应缺陷表型。生化分析表明，TRAIP的N端是RAP80相互作用的关键，而TRAIP的C端是TRAIP通过与RNF20-RNF40直接作用定位DNA损伤部位所必需的。综上所述，我们的发现表明，新的RAP80结合伙伴TRAIP调节损伤信号机制的招募，并促进同源重组。将DNA损伤修复因子招募到DNA损伤部位是维持基因组完整性的关键。在这里，作者发现TRAF相互作用蛋白(TRAIP/RNF206)是RAP80正常募集到DNA损伤和刺激同源重组所必需的。
RAP80 localizes to sites of DNA insults to enhance the DNA-damage responses. Here we identify TRAIP/RNF206 as a novel RAP80-interacting protein and find that TRAIP is necessary for translocation of RAP80 to DNA lesions. Depletion of TRAIP results in impaired accumulation of RAP80 and functional downstream partners, including BRCA1, at DNA lesions. Conversely, accumulation of TRAIP is normal in RAP80-depleted cells, implying that TRAIP acts upstream of RAP80 recruitment to DNA lesions. TRAIP localizes to sites of DNA damage and cells lacking TRAIP exhibit classical DNA-damage response-defect phenotypes. Biochemical analysis reveals that the N terminus of TRAIP is crucial for RAP80 interaction, while the C terminus of TRAIP is required for TRAIP localization to sites of DNA damage through a direct interaction with RNF20–RNF40. Taken together, our findings demonstrate that the novel RAP80-binding partner TRAIP regulates recruitment of the damage signalling machinery and promotes homologous recombination. Recruiting DNA damage repair factors to the sites of DNA damage is critical for the maintenance of genome integrity. Here the authors identify that the TRAF-interacting protein (TRAIP/RNF206) is required for normal recruitment of RAP80 to DNA lesions and the stimulation of homologous recombination.