Extensive DNA Damage-Induced Sumoylation Contributes to Replication and Repair and Acts in Addition to the Mec1 Checkpoint

被引：164

作者：

Cremona, Catherine A. ^{[1
]}

Sarangi, Prabha ^{[1
,2
,3
,4
]}

Yang, Yan ^{[1
]}

Hang, Lisa E. ^{[1
,2
,3
,4
]}

Rahman, Sadia ^{[1
]}

Zhao, Xiaolan ^{[1
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10065 USA

[2] Weill Cornell Grad Sch Med Sci, Programs Biochem, New York, NY 10065 USA

[3] Weill Cornell Grad Sch Med Sci, Cell Biol Program, New York, NY 10065 USA

[4] Weill Cornell Grad Sch Med Sci, Program Mol Biol, New York, NY 10065 USA

来源：

MOLECULAR CELL | 2012年 / 45卷 / 03期

关键词：

S-PHASE CHECKPOINT; SACCHAROMYCES-CEREVISIAE; BUDDING YEAST; HOMOLOGOUS RECOMBINATION; SUMO MODIFICATIONS; UBIQUITIN; COMPLEX; BREAKS; PHOSPHORYLATION; PROTEINS;

D O I：

10.1016/j.molcel.2011.11.028

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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.

引用

页码：422 / 432

页数：11

共 53 条

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