The human checkpoint sensor Rad9-Rad1-Hus1 interacts with and stimulates NEIL1 glycosylase
The human checkpoint sensor Rad9-Rad1-Hus1 interacts with and stimulates NEIL1 glycosylase
复制标题
DOI：
10.1093/nar/gkm075
复制
发表时间：
2007-04-01
影响因子：
14.9
通讯作者：
Lu, A-Lien
中科院分区：
文献类型：
--
作者：
Guan, Xin;Bai, Haibo;Lu, A-Lien
检查点蛋白Rad 9/Rad 1/Hus 1异源三聚体（9-1-1复合物）在结构上类似于增殖细胞核抗原滑动钳，并已被提出用于检测导致细胞周期停滞或凋亡的DNA损伤。人（h）NEIL 1 DNA糖基化酶是细菌Nei/Fpg的直向同源物，参与修复氧化损伤的DNA碱基。在这项研究中，我们表明，hNEIL 1相互作用的hRad 9，hRad 1和hHus 1作为单独的蛋白质和作为一个复杂的。hNEIL 1的290 - 350位残基对于9-1-1结合是重要的。在过氧化氢处理的细胞中，hNEIL 1核灶的显著部分与hRad 9灶共定位。人NEIL 1 DNA糖基化酶活性分别被hHus 1、hRad 1、hRad 9和9-1-1复合物显著刺激。因此，在病变部位的9-1-1复合物作为损伤传感器激活检查点控制和碱基切除修复的组成部分。
The checkpoint protein Rad9/Rad1/Hus1 heterotrimer (the 9-1-1 complex) is structurally similar to the proliferating cell nuclear antigen sliding clamp and has been proposed to sense DNA damage that leads to cell cycle arrest or apoptosis. Human (h) NEIL1 DNA glycosylase, an ortholog of bacterial Nei/Fpg, is involved in repairing oxidatively damaged DNA bases. In this study, we show that hNEIL1 interacts with hRad9, hRad1 and hHus1 as individual proteins and as a complex. Residues 290 350 of hNEIL1 are important for the 9-1-1 association. A significant fraction of the hNEIL1 nuclear foci co-localize with hRad9 foci in hydrogen peroxide treated cells. Human NEIL1 DNA glycosylase activity is significantly stimulated by hHus1, hRad1, hRad9 separately and the 9-1-1 complex. Thus, the 9-1-1 complex at the lesion sites serves as both a damage sensor to activate checkpoint control and a component of base excision repair.