Key Laboratory of Arrhythmias, Ministry of Education, and Institute of Medical Genetics, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
J Biol Chem. 2011 Aug 12;286(32):28192-9. doi: 10.1074/jbc.M111.258087. Epub 2011 Jun 24.
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.
DNA 损伤检查点 1 （MDC1）的介质在 DNA 损伤反应（DDR）中起着重要作用。MDC1 作为一种中介蛋白，可与参与 DDR 不同方面的多种蛋白结合。然而，关于 MDC1 复合物的组成知之甚少。在这里，我们发现，在 DNA 损伤后，共济失调毛细血管扩张症突变（ATM）可使 MDC1 的 Thr-98 发生磷酸化，从而促进其寡聚化。MDC1 的寡聚化对于 MDC1 复合物在 DNA 损伤部位的积累很重要。Thr-98（T98A）的突变会使其寡聚化，导致 DNA 损伤检查点激活缺陷和对辐射的敏感性增加。总之，这些结果表明 MDC1 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。
