Rad53 FHA domain associated with phosphorylated Rad9 in the DNA damage checkpoint
Rad53 FHA domain associated with phosphorylated Rad9 in the DNA damage checkpoint
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DOI：
10.1126/science.281.5374.272
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发表时间：
1998-07-10
期刊：
影响因子：
56.9
通讯作者：
Stern, DF
中科院分区：
文献类型：
--
作者：
Sun, ZX;Hsiao, J;Stern, DF
酿酒酵母的Rad 53蛋白激酶是阻止具有受损或不完全复制的DNA的细胞中的细胞分裂的检查点所必需的。Rad 9蛋白响应于DNA损伤而被磷酸化，并且磷酸化的Rad 9与Rad 53的COOH-末端叉头同源相关（FHA）结构域相互作用，该结构域的失活消除了DNA损伤依赖的Rad 53磷酸化，G2/M细胞周期阻滞，RNR 3转录增加，但不影响复制抑制依赖性的Rad 53磷酸化，因此，Rad 53通过与磷酸化的Rad 9偶联整合DNA损伤信号，迄今为止尚未表征的FHA结构域似乎是模块化蛋白结合结构域。
The Rad53 protein kinase of Saccharomyces cerevisiae is required for checkpoints that prevent cell division in cells with damaged or incompletely replicated DNA, The Rad9 protein was phosphorylated in response to DNA damage, and phosphorylated Rad9 interacted with the COOH-terminal forkhead homology-associated (FHA) domain of Rad53, Inactivation of this domain abolished DNA damage-dependent Rad53 phosphorylation, G(2)/M cell cycle phase arrest, and increase of RNR3 transcription but did not affect replication inhibition-dependent Rad53 phosphorylation, Thus, Rad53 integrates DNA damage signals by coupling with phosphorylated Rad9, The hitherto uncharacterized FHA domain appears to be a modular protein-binding domain.