Wang Jean Y J, Edelmann Winfried
Division of Hematology/Oncology, Department of Medicine and Moores Cancer Center, University of California, San Diego, School of Medicine, 3855 Health Sciences Drive, La Jolla, California 92093, USA.
Cancer Cell. 2006 Jun;9(6):417-8. doi: 10.1016/j.ccr.2006.05.013.
The DNA mismatch repair (MMR) system maintains genome integrity by correcting replication errors. MMR also stimulates checkpoint and cell death responses to DNA damage suggested by the resistance of MMR-defective tumor cells to several chemotherapeutic agents. MMR-dependent cytotoxic response may result from futile repair; however, MMR-mediated apoptosis has been genetically separated from its repair function. In a recent issue of Molecular Cell, Yoshioka and coworkers show that MMR complexes (MutSalpha and MutLalpha) are required for the recruitment of ATR-ATRIP to sites of alkylation damage, demonstrating that MMR complexes can function as sensors in DNA damage signal transduction.
DNA错配修复（MMR）系统通过纠正复制错误来维持基因组完整性。MMR还能刺激对DNA损伤的检查点和细胞死亡反应，这一点由MMR缺陷型肿瘤细胞对几种化疗药物的抗性所表明。MMR依赖的细胞毒性反应可能源于无效修复；然而，MMR介导的细胞凋亡在遗传上已与其修复功能分离。在最近一期的《分子细胞》杂志上，吉冈及其同事表明，MMR复合物（MutSα和MutLα）是将ATR-ATRIP招募到烷基化损伤位点所必需的，这表明MMR复合物可在DNA损伤信号转导中充当传感器。
