Rad9通过与MLH1的物理相互作用在DNA错配修复中发挥重要作用。

He Wei, Zhao Yun, Zhang Chunbo, An Lili, Hu Zhishang, Liu Yuheng, Han Lu, Bi Lijun, Xie Zhensheng, Xue Peng, Yang Fuquan, Hang Haiying

National Laboratory of Biomacromolecules, Center for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

Nucleic Acids Res. 2008 Nov;36(20):6406-17. doi: 10.1093/nar/gkn686. Epub 2008 Oct 8.

Rad9 is conserved from yeast to humans and plays roles in DNA repair (homologous recombination repair, and base-pair excision repair) and cell cycle checkpoint controls. It has not previously been reported whether Rad9 is involved in DNA mismatch repair (MMR). In this study, we have demonstrated that both human and mouse Rad9 interacts physically with the MMR protein MLH1. Disruption of the interaction by a single-point mutation in Rad9 leads to significantly reduced MMR activity. This disruption does not affect S/M checkpoint control and the first round of G(2)/M checkpoint control, nor does it alter cell sensitivity to UV light, gamma rays or hydroxyurea. Our data indicate that Rad9 is an important factor in MMR and carries out its MMR function specifically through interaction with MLH1.

Rad9从酵母到人类都保守存在，在DNA修复（同源重组修复和碱基切除修复）及细胞周期检查点控制中发挥作用。此前尚无关于Rad9是否参与DNA错配修复（MMR）的报道。在本研究中，我们证明人类和小鼠的Rad9均与MMR蛋白MLH1发生物理相互作用。Rad9中的单点突变导致这种相互作用中断，进而使MMR活性显著降低。这种中断不影响S/M检查点控制和第一轮G(2)/M检查点控制，也不改变细胞对紫外线、γ射线或羟基脲的敏感性。我们的数据表明，Rad9是MMR中的一个重要因子，并且通过与MLH1相互作用特异性地执行其MMR功能。