Rad9 phosphorylation sites couple Rad53 to the Saccharomyces cerevisiae DNA damage checkpoint
Rad9 phosphorylation sites couple Rad53 to the Saccharomyces cerevisiae DNA damage checkpoint
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DOI：
10.1016/s1097-2765(02)00532-4
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发表时间：
2002-05-01
期刊：
影响因子：
16
通讯作者：
Stern, DF
中科院分区：
文献类型：
--
作者：
Schwartz, MF;Duong, JK;Stern, DF
Rad 9是由Rad 53和Chk 1介导的MEC 1/TEL 1依赖性激活酿酒酵母DNA损伤检查点途径所必需的。DNA损伤诱导Rad 9磷酸化，并且Rad 53特异性地与磷酸化的Rad 9缔合。我们在这里报告说，多个Mec 1/Tel 1共识[S/T]Q网站内Rad 9磷酸化的DNA损伤。这些Rad 9磷酸化位点是激活检查点途径的Rad 53分支所选择性需要的。与体内招募Rad 53的功能一致，Rad 9磷酸肽在体外被Rad 53叉头相关（FHA）结构域结合。这些数据表明，Rad 9内功能独立的结构域调节Rad 53和Chk 1，并支持FHA结构域介导的Rad 9磷酸肽识别将Rad 53与DNA损伤检查点途径偶联的模型。
Rad9 is required for the MEC1/TEL1-dependent activation of Saccharomyces cerevisiae DNA damage checkpoint pathways mediated by Rad53 and Chk1. DNA damage induces Rad9 phosphorylation, and Rad53 specifically associates with phosphorylated Rad9. We report here that multiple Mec1/Tel1 consensus [S/T]Q sites within Rad9 are phosphorylated in response to DNA damage. These Rad9 phosphorylation sites are selectively required for activation of the Rad53 branch of the checkpoint pathway. Consistent with the in vivo function in recruiting Rad53, Rad9 phosphopeptides are bound by Rad53 forkhead-associated (FHA) domains in vitro. These data suggest that functionally independent domains within Rad9 regulate Rad53 and Chk1, and support the model that FHA domain-mediated recognition of Rad9 phosphopeptides couples Rad53 to the DNA damage checkpoint pathway.