Extensive DNA damage-induced sumoylation contributes to replication and repair and acts in addition to the mec1 checkpoint.
Extensive DNA damage-induced sumoylation contributes to replication and repair and acts in addition to the mec1 checkpoint.
复制标题
DOI：
10.1016/j.molcel.2011.11.028
复制
发表时间：
2012-02-10
期刊：
影响因子：
16
通讯作者：
Zhao, Xiaolan
中科院分区：
文献类型：
--
作者：
Cremona, Catherine A.;Sarangi, Prabha;Yang, Yan;Hang, Lisa E.;Rahman, Sadia;Zhao, Xiaolan
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作用。大量的工作已经详细说明了典型的检查点介导的磷酸化在这个程序中的作用。最近的研究也暗示sumoylation在DNA损伤反应，但是，一个系统的观点sumoylation的复制和修复的贡献，其与检查点的相互作用是缺乏的。在这里，使用酵母中的生化筛选，我们建立了DNA损伤诱导的类小泛素化发生在大规模。我们确定MRX（Mre 11-Rad 50-Xrs 2）作为修复靶点子集的这种诱导的正调节因子。此外，我们发现有缺陷的SUMO化导致受损基因组无法完成复制，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损伤诱导的类小泛素化不需要Mec 1检查点信号，两者的存在使最佳的DNA损伤抗性。
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.
登录
查看更多内容
影响因子：
16.8
作者：
通讯作者：
--
影响因子：
64.5
作者：
Johnson, ES;Gupta, AA
通讯作者：
Gupta, AA
影响因子：
5.3
作者：
Chen, XL;Reindle, A;Johnson, ES
通讯作者：
Johnson, ES
影响因子：
11.4
作者：
Mimitou, Eleni P.;Symington, Lorraine S.
通讯作者：
Symington, Lorraine S.
影响因子：
64.8
作者：
通讯作者：
--