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首页> 外文期刊>Molecular cell >Extensive DNA Damage-Induced Sumoylation Contributes to Replication and Repair and Acts in Addition to the Mec1 Checkpoint
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Extensive DNA Damage-Induced Sumoylation Contributes to Replication and Repair and Acts in Addition to the Mec1 Checkpoint

机译:广泛的DNA损伤诱导的Sumoylation有助于复制和修复,并作为Mec1检查点的补充。

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摘要

The cellular response to DNA damage employs multiple dynamic protein modifications to exert rapid and adaptable effects. Substantial work has detailed the roles of canonical checkpoint-mediated phosphorylation in this program. Recent studies have also implicated sumoylation in the DNA damage response; however, a systematic view of the contribution of sumoylation to replication and repair and its interplay with checkpoints is lacking. Here, using a biochemical screen in yeast, we establish that DNA damage-induced sumoylation occurs on a large scale. We identify MRX (Mre11-Rad50-Xrs2) as a positive regulator of this induction for a subset of repair targets. In addition, we find that defective sumoylation results in failure to complete replication of a damaged genome and impaired DNA end processing, highlighting the importance of the SUMO-mediated response in genome integrity. We also show that DNA damage-induced sumoylation does not require Mec1 checkpoint signaling, and the presence of both enables optimal DNA damage resistance.
机译:细胞对DNA损伤的反应利用多种动态蛋白质修饰来发挥快速和适应性的作用。大量工作详细说明了该程序中规范检查点介导的磷酸化的作用。最近的研究还表明在DNA损伤反应中存在磺酰化作用。然而,缺乏对磺酰化对复制和修复的贡献及其与检查点之间相互作用的系统性认识。在这里,使用酵母中的生化筛选,我们确定DNA损伤诱导的sumoylation大规模发生。我们确定MRX(Mre11-Rad50-Xrs2)作为这一诱导的修复目标子集的积极监管者。此外,我们发现有缺陷的sumoyation导致无法完成损坏的基因组的完全复制和受损的DNA最终处理,突出显示SUMO介导的反应在基因组完整性中的重要性。我们还表明,DNA损伤诱导的sumoylation不需要Mec1检查点信号,并且两者的存在都能实现最佳的DNA损伤抗性。

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