生物
G2-M DNA损伤检查点
DNA复制因子CDT1
细胞生物学
原点识别复合体
DNA复制
染色质重塑
复制因子C
染色体复制控制
复制前复合体
染色质
遗传学
微小染色体维持
复制蛋白A
作者
Tracey J. Au,Jairo Rodriguez,Jack A. Vincent,Toshio Tsukiyama
摘要
The S phase checkpoint response slows down replication in the presence of replication stress such that replication can resume normally once conditions are favorable. Both proper activation and deactivation of the checkpoint are crucial for genome stability. However, the mechanisms of checkpoint deactivation have been largely unknown. Here, we show that two highly conserved Saccharomyces cerevisiae ATP-dependent chromatin remodeling factors, Isw2 and Ino80, function to attenuate and deactivate S phase checkpoint activity. Genetic interactions revealed that these chromatin remodeling factors and the Rad53 phosphatases function in parallel in the DNA replication stress response. Following a transient replication stress, an isw2 nhp10 double mutant displays stronger and prolonged checkpoint activation without experiencing increased replication fork troubles. Isw2 and Ino80 are both enriched at stalled replication forks and physically and specifically interact with a single-stranded DNA binding protein, replication protein A (RPA). Based on these results, we propose that Isw2 and Ino80 are targeted to stalled replication forks via RPA and directly control the amplitude of S phase checkpoint activity and the subsequent deactivation process.
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