Chk1 activation requires Rad9 S/TQ-site phosphorylation to promote association with C-terminal BCRT domains of Rad4TOPBP1

被引：132

作者：

Furuya, K ^{[1
]}

Poitelea, M ^{[1
]}

Guo, L ^{[1
]}

Caspari, T ^{[1
]}

Carr, AM ^{[1
]}

机构：

[1] Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England

来源：

GENES & DEVELOPMENT | 2004年 / 18卷 / 10期

基金：

英国医学研究理事会;

关键词：

checkpoint; DNA replication; fission yeast; DNA damage; ATR;

D O I：

10.1101/gad.291104

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

To gain insight into the function and organization of proteins assembled on the DNA in response to genotoxic insult we investigated the phosphorylation of the Schizosaccharomyces pombe PCNA-like checkpoint protein Rad(9). C-terminal T412/S423 phosphorylation of Rad9 by Rad3(ATR) occurs in S phase without replication stress. Rad3(ATR) and Tel1(ATM) phosphorylate these same residues, plus additional ones, in response to DNA damage. In S phase and after damage, only Rad9 phosphorylated on T412/S423, but not unphosphorylated Rad9, associates with a two-BRCT-domain region of the essential Rad4(TOPBP1) protein. Rad9-Rad4(TOPBP1) interaction is required to activate the Chk1 damage checkpoint but not the Cds1 replication checkpoint. When the Rad9-T412/S423 are phosphorylated, Rad4(TOPBP1) coprecipitates with Rad3(ATR), suggesting that phosphorylation coordinates formation of an active checkpoint complex.

引用

页码：1154 / 1164

页数：11