广泛的 DNA 损伤诱导的 SUMO 化有助于复制和修复，并与 mec1 检查点一起发挥作用。
Extensive DNA damage-induced sumoylation contributes to replication and repair and acts in addition to the mec1 checkpoint.
机构信息
Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
出版信息
Mol Cell. 2012 Feb 10;45(3):422-32. doi: 10.1016/j.molcel.2011.11.028. Epub 2012 Jan 26.
Abstract
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.
摘要
细胞对 DNA 损伤的反应采用多种动态蛋白质修饰来发挥快速和适应性的效应。大量的工作详细描述了规范检查点介导的磷酸化在这一程序中的作用。最近的研究也表明，SUMO 化参与了 DNA 损伤反应；然而，SUMO 化对复制和修复的贡献及其与检查点的相互作用的系统观点尚缺乏。在这里，我们使用酵母的生化筛选，确定了 DNA 损伤诱导的 SUMO 化在很大程度上发生。我们确定 MRX（Mre11-Rad50-Xrs2）是一组修复靶标的这种诱导的正调节剂。此外，我们发现有缺陷的 SUMO 化导致受损基因组的复制无法完成和 DNA 末端加工受损，突出了 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 SUMO 化不需要 Mek1 检查点信号，并且两者的存在都能使 DNA 损伤抗性达到最佳。
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