A role for the arginine methylation of Rad9 in checkpoint control and cellular sensitivity to DNA damage
A role for the arginine methylation of Rad9 in checkpoint control and cellular sensitivity to DNA damage
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DOI：
10.1093/nar/gkq1264
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发表时间：
2011-06-01
影响因子：
14.9
通讯作者：
Hang, Haiying
中科院分区：
文献类型：
--
作者：
He, Wei;Ma, Xiaoyan;Hang, Haiying
基因组的稳定性是通过DNA修复和检查点的协调行动来维持的，这些检查点推迟了细胞周期中对DNA损伤的反应。RAD9从酵母到人类都是保守的，并在细胞周期检查点控制中发挥作用。在这里，报告了一种对Rad9功能的调节机制。在这项研究中，RAD9被发现与蛋白质精氨酸甲基转移酶5(PRMT5)相互作用并被其甲基化。RAD9的精氨酸甲基化在S/M和G2/M细胞周期检查点中起关键作用。在只表达不能甲基化的突变Rad9的细胞中，Rad9下游检查点效应器Chk1的激活受到损害。此外，RAD9甲基化也是细胞抵抗DNA损伤压力所必需的。综上所述，我们发现精氨酸甲基化对于调节Rad9的功能是重要的，因此是维持基因组完整性的主要因素。
The genome stability is maintained by coordinated action of DNA repairs and checkpoints, which delay progression through the cell cycle in response to DNA damage. Rad9 is conserved from yeast to human and functions in cell cycle checkpoint controls. Here, a regulatory mechanism for Rad9 function is reported. In this study Rad9 has been found to interact with and be methylated by protein arginine methyltransferase 5 (PRMT5). Arginine methylation of Rad9 plays a critical role in S/M and G2/M cell cycle checkpoints. The activation of the Rad9 downstream checkpoint effector Chk1 is impaired in cells only expressing a mutant Rad9 that cannot be methylated. Additionally, Rad9 methylation is also required for cellular resistance to DNA damaging stresses. In summary, we uncovered that arginine methylation is important for regulation of Rad9 function, and thus is a major element for maintaining genome integrity.