Molecular Cell
Volume 45, Issue 3, 10 February 2012, Pages 422-432
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Article
Extensive DNA Damage-Induced Sumoylation Contributes to Replication and Repair and Acts in Addition to the Mec1 Checkpoint

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Summary

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.

Highlights

► DNA damage-induced sumoylation (DDIS) occurs on a large scale ► DDIS does not depend on the Mec1 checkpoint for activation ► Sumoylation induction exhibits modularity; MRX controls a subset of repair targets ► Defective sumoylation impairs replication and blocks processing of DNA ends.

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3

Present address: New York University School of Medicine, New York, NY 10016, USA

4

Present address: Gerstner Sloan-Kettering Graduate School of Biomedical Sciences, New York, NY 10065, USA