Foster Steven S, Zubko Mikhajlo K, Guillard Sandrine, Lydall David
Institute for Ageing and Health, University of Newcastle, Henry Wellcome Laboratory for Biogerontology Research, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE, UK.
DNA Repair (Amst). 2006 Jul 13;5(7):840-51. doi: 10.1016/j.dnarep.2006.04.005. Epub 2006 Jun 12.
MRX, an evolutionally conserved DNA damage response complex composed of Mre11, Rad50 and Xrs2, is involved in DNA double strand break (DSB) repair, checkpoint activation and telomere maintenance. At DSBs, MRX plays a role in generating single stranded DNA (ssDNA) and signalling cell cycle arrest. Here we investigated whether MRX also contributes to generating ssDNA or signalling cell cycle arrest at uncapped telomeres. To investigate the role of MRX, we generated a conditionally degradable Rad50 protein and combined this with cdc13-1, a temperature sensitive mutation in the Cdc13 telomere capping protein. We show that Rad50 does not contribute to ssDNA generation or cell cycle arrest in response to cdcl3-1 uncapped telomeres. Instead, we find that Rad50 inhibits ssDNA accumulation and promotes cdc13-1 cell viability, consistent with a major role for MRX in telomere capping.
MRX是一种由Mre11、Rad50和Xrs2组成的进化保守的DNA损伤反应复合物，参与DNA双链断裂（DSB）修复、检查点激活和端粒维持。在DSB处，MRX在生成单链DNA（ssDNA）和发出细胞周期停滞信号方面发挥作用。在这里，我们研究了MRX是否也有助于在无帽端粒处生成ssDNA或发出细胞周期停滞信号。为了研究MRX的作用，我们生成了一种条件可降解的Rad50蛋白，并将其与cdc13-1（端粒封盖蛋白Cdc13中的温度敏感突变）相结合。我们发现，Rad50对响应cdc13-1无帽端粒时的ssDNA生成或细胞周期停滞没有贡献。相反，我们发现Rad50抑制ssDNA积累并促进cdc13-1细胞活力，这与MRX在端粒封盖中的主要作用一致。
