Esc4p, a new target of Mec1p (ATR), promotes resumption of DNA synthesis after DNA damage

被引:75
作者
Rouse, J [1 ]
机构
[1] Univ Dundee, MRC, Prot Phosphorylat Unit, Wellcome Trust Bioctr,Med Sci Inst, Dundee DD1 4HN, Scotland
关键词
ATR; DNA damage; Esc4p; Mec1p;
D O I
10.1038/sj.emboj.7600129
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The DNA damage-responsive protein kinases ATM and ATR phosphorylate SQ/TQ motifs that lie in clusters in most of their in vivo targets. Budding yeast Esc4p contains a cluster of SQ/TQ motifs, suggesting that it might be a target of Mec1p/Tel1p (yeast ATR/ATM). Here it is reported that Esc4p is phosphorylated by Mec1p in response to DNA damage during DNA replication and that cells lacking Esc4p are hypersensitive to DNA damage specifically during S phase. Esc4p is not required for the intraS-phase checkpoint but is essential for resumption of chromosome replication after DNA damage, and its role in promoting restart appears to be distinct from that of Rad53p. Mutation of Esc4p SQ/TQ motifs phosphorylated by Mec1p or mutation of the BRCT domains of Esc4p also renders cells unable to restart DNA replication after DNA damage and causes hypersensitivity to genotoxins. These results identify Esc4p as an important new S-phase-specific target of Mec1p.
引用
收藏
页码:1188 / 1197
页数:10
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