ATR/Mec1: coordinating fork stability and repair

被引:114
作者
Friedel, Anna M. [1 ]
Pike, Brietta L. [1 ]
Gasser, Susan M. [1 ]
机构
[1] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland
基金
瑞士国家科学基金会;
关键词
DNA-DAMAGE CHECKPOINT; DOUBLE-STRAND BREAK; STALLED REPLICATION FORKS; S-PHASE CHECKPOINT; SACCHAROMYCES-CEREVISIAE; BUDDING YEAST; DEPENDENT PHOSPHORYLATION; GENOME INSTABILITY; DISTINCT ROLES; MEC1; KINASE;
D O I
10.1016/j.ceb.2009.01.017
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
During S phase, eukaryotic cells unwind and duplicate a tremendous amount of DNA, generating structures that are very sensitive to both endogenous and exogenous insults. The collision of DNA polymerases with damaged DNA or other obstructions to fork progression generates replication stress, which can evolve into fork collapse if the replisome components are not stabilized. To ensure gnome integrity, stalled replication forks are recognized by a checkpoint, whose central player is the human kinase ATR or Mec1 in S. cerevisiae. This review will discuss recent findings revealing roles of the ATIR/Mec1 kinase: both in stabilizing the replisome directly and in activating the checkpoint response to regulate origin firing, DNA repair, fork restart, and cell cycle progression.
引用
收藏
页码:237 / 244
页数:8
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