Oligomerization of MDC1 Protein Is Important for Proper DNA Damage Response
Oligomerization of MDC1 Protein Is Important for Proper DNA Damage Response
复制标题
MDC1 蛋白的寡聚化对于正确的 DNA 损伤反应很重要
DOI：
10.1074/jbc.m111.258087
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发表时间：
2011-08-12
影响因子：
4.8
通讯作者：
Lou, Zhenkun
中科院分区：
文献类型：
--
作者：
Luo, Kuntian;Yuan, Jian;Lou, Zhenkun
DNA损伤检查点介导因子1（Mediator of DNA damage checkpoint 1，MDC 1）在DNA损伤反应（DNA damage response，DDR）中起重要作用。MDC 1作为介体蛋白发挥作用，并结合参与DDR不同方面的多种蛋白质。然而，对MDC 1复合物的组织知之甚少。在这里，我们表明共济失调毛细血管扩张症，突变（ATM）磷酸化MDC 1在Thr-98后，DNA损伤，这促进其寡聚化。MDC 1的寡聚化对于MDC 1复合物在DNA损伤位点的积累是重要的。Thr-98（T98 A）突变将消除其寡聚化，导致DNA损伤检查点激活缺陷和对辐射的敏感性增加。综上所述，这些结果表明，MDC 1的寡聚化在DDR中起着重要作用，并有助于理解DNA损伤部位蛋白质复合物的形成。
Mediator of DNA damage checkpoint 1 (MDC1) plays an important role in the DNA damage response (DDR). MDC1 functions as a mediator protein and binds multiple proteins involved in different aspects of the DDR. However, little is know about the organization of MDC1 complexes. Here we show that ataxia telangiectasia, mutated (ATM) phosphorylates MDC1 at Thr-98 following DNA damage, which promotes its oligomerization. Oligomerization of MDC1 is important for the accumulation of MDC1 complex at the sites of DNA damage. Mutation of Thr-98 (T98A) would abolish its oligomerization and result in a defect in DNA damage checkpoint activation and increased sensitivity to irradiation. Taken together, these results suggest that the oligomerization of MDC1 plays an important role in DDR and help understand the formation of proteins complexes at the sites of DNA damage.