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首页> 外文期刊>Molecular and Cellular Biology >ATP-Dependent Chromatin Remodeling Factors Tune S Phase Checkpoint Activity
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ATP-Dependent Chromatin Remodeling Factors Tune S Phase Checkpoint Activity

机译：ATP依赖性染色质重塑因子，可调节S期检查点活性

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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.
机译：在存在复制压力的情况下，S阶段检查点响应会减慢复制速度，以便一旦条件良好即可正常恢复复制。检查点的正确激活和去激活对于基因组稳定性都是至关重要的。但是，检查点停用的机制在很大程度上尚不清楚。在这里，我们显示了两个高度保守的酿酒酵母ATP依赖的染色质重塑因子Isw2和Ino80，可减弱和灭活S期检查点的活性。遗传相互作用表明，这些染色质重塑因子和Rad53磷酸酶在DNA复制应激反应中平行发挥作用。在短暂的复制压力下， isw2 nhp10 双重突变体显示出更强和更长的检查点激活，而没有遇到增加的复制叉问题。 Isw2和Ino80都在停滞的复制叉处富集，并且在物理上和特异性地与单链DNA结合蛋白复制蛋白A（RPA）相互作用。根据这些结果，我们建议Isw2和Ino80通过RPA定位于停滞的复制叉，并直接控制S相检查点活动的幅度以及随后的停用过程。

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