National Laboratory of Biomacromolecules, and the Center for Computational and Systems Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Protein Cell. 2011 May;2(5):410-22. doi: 10.1007/s13238-011-1049-7. Epub 2011 Jun 2.
The Rad1 gene is evolutionarily conserved from yeast to human. The fission yeast Schizosaccharomyces pombe Rad1 ortholog promotes cell survival against DNA damage and is required for G(2)/M checkpoint activation. In this study, mouse embryonic stem (ES) cells with a targeted deletion of Mrad1, the mouse ortholog of this gene, were created to evaluate its function in mammalian cells. Mrad1 (-/-) ES cells were highly sensitive to ultraviolet-light (UV light), hydroxyurea (HU) and gamma rays, and were defective in G(2)/M as well as S/M checkpoints. These data indicate that Mrad1 is required for repairing DNA lesions induced by UV-light, HU and gamma rays, and for mediating G(2)/M and S/M checkpoint controls. We further demonstrated that Mrad1 plays an important role in homologous recombination repair (HRR) in ES cells, but a minor HRR role in differentiated mouse cells.
Rad1 基因从酵母到人类在进化上是保守的。裂殖酵母 Schizosaccharomyces pombe 的 Rad1 同源物促进细胞存活以对抗 DNA 损伤，并需要 G(2)/M 检查点激活。在这项研究中，创建了靶向缺失 Mrad1（该基因的小鼠同源物）的小鼠胚胎干细胞 (ES) 细胞，以评估其在哺乳动物细胞中的功能。Mrad1(-/-) ES 细胞对紫外线 (UV 光)、羟基脲 (HU) 和伽马射线高度敏感，并且在 G(2)/M 和 S/M 检查点都有缺陷。这些数据表明 Mrad1 是修复由 UV 光、HU 和伽马射线诱导的 DNA 损伤以及介导 G(2)/M 和 S/M 检查点控制所必需的。我们进一步证明 Mrad1 在 ES 细胞中的同源重组修复 (HRR) 中发挥重要作用，但在分化的小鼠细胞中 HRR 作用较小。
