Linkage of ATM to cell cycle regulation by the Chk2 protein kinase
Linkage of ATM to cell cycle regulation by the Chk2 protein kinase
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DOI：
10.1126/science.282.5395.1893
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发表时间：
1998-12-04
期刊：
影响因子：
56.9
通讯作者：
Elledge, SJ
中科院分区：
文献类型：
--
作者：
Matsuoka, S;Huang, MX;Elledge, SJ
为了应对DNA损伤和复制障碍，线圈通过控制关键的细胞周期调节因子来阻止细胞周期的进展，我们确定了Chk2，这是酿酒酵母Rad53和庞氏裂殖酵母CDs1蛋白的哺乳动物同源物，是DNA损伤和复制检查点所需的。Chk2被迅速磷酸化并被激活，以响应复制阻断和DNA损伤；对DNA损伤的响应以依赖于共济失调的毛细血管扩张突变(ATM)的方式发生。在体外，Chk2磷酸化了丝氨酸-216上的CDc25C，这是一个已知参与CDc25C负调控的位置。这与蛋白激酶Chk1磷酸化的位置相同，这表明，作为对DNA损伤和DNA复制压力的反应，Chk1和Chk2可能会磷酸化CDc25C，以阻止进入有丝分裂。
In response to DNA damage and replication blocks, coils prevent cell cycle progression through the control of critical cell cycle regulators, We identified Chk2, the mammalian homolog of the Saccharomyces cerevisiae Rad53 and Schizosaccharomyces pombe Cds1 protein kinases required for the DNA damage and replication checkpoints. Chk2 was rapidly phosphorylated and activated in response to replication blocks and DNA damage; the response to DNA damage occurred in an ataxia telangiectasia mutated (ATM)-dependent manner. In vitro, Chk2 phosphorylated Cdc25C on serine-216, a site known to be involved in negative regulation of Cdc25C. This is the same site phosphorylated by the protein kinase Chk1, which suggests that, in response to DNA damage and DNA replicational stress, Chk1 and Chk2 may phosphorylate Cdc25C to prevent entry into mitosis.