Schwartz Marc F, Duong Jimmy K, Sun Zhaoxia, Morrow Jon S, Pradhan Deepti, Stern David F
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA.
Mol Cell. 2002 May;9(5):1055-65. doi: 10.1016/s1097-2765(02)00532-4.
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.
Rad9是酿酒酵母DNA损伤检查点途径由Rad53和Chk1介导的MEC1/TEL1依赖性激活所必需的。DNA损伤诱导Rad9磷酸化,并且Rad53特异性地与磷酸化的Rad9结合。我们在此报告,Rad9内多个Mec1/Tel1共有[S/T]Q位点在DNA损伤响应中被磷酸化。这些Rad9磷酸化位点对于检查点途径的Rad53分支的激活是选择性必需的。与在体内招募Rad53的功能一致,Rad9磷酸肽在体外被Rad53叉头相关(FHA)结构域结合。这些数据表明Rad9内功能独立的结构域调节Rad53和Chk1,并支持FHA结构域介导的对Rad9磷酸肽的识别将Rad53与DNA损伤检查点途径偶联的模型。