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PMID: 20705237 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Regulation of DNA repair through deSUMOylation and SUMOylation of replication protein A complex.

Molecular cell ·Vol. 39 ·No. 3 ·2010-08-13 ·Pages 333-45

Dou H, Huang C, Singh M, Carpenter PB, Yeh ET

Abstract

The replication protein A complex (RPA) plays a crucial role in DNA replication and damage response. However, it is not known whether this complex is regulated by the SUMOylation pathway. Here, we show that the 70 kDa subunit of RPA (RPA70) associates with a Sentrin/SUMO-specific protease, SENP6, in the nucleus to maintain RPA70 in a hypoSUMOylated state during S phase. Campothecin (CPT), an inducer of replication stress, dissociates SENP6 from RPA70, allowing RPA70 to be modified by a small ubiquitin-like modifier 2/3 (SUMO-2/3). RPA70 SUMOylation facilitates recruitment of Rad51 to the DNA damage foci to initiate DNA repair through homologous recombination (HR). Cell lines that expressed a RPA70 mutant that cannot be SUMOylated are defective in HR and have a marked increase in sensitivity to CPT. These results demonstrate that SUMOylation status of RPA70 plays a critical role in the regulation of DNA repair through homologous recombination.

MeSH Terms
Cell Line Cysteine Endopeptidases/genetics,metabolism DNA Repair/physiology DNA Replication/physiology DNA-Directed DNA Polymerase/genetics,metabolism Humans Multienzyme Complexes/genetics,metabolism Mutation Protein Processing, Post-Translational/physiology Recombination, Genetic/physiology Replication Protein A/genetics,metabolism S Phase/physiology Small Ubiquitin-Related Modifier Proteins/genetics,metabolism Ubiquitins/genetics,metabolism
Chemicals
Multienzyme Complexes RPA1 protein, human Replication Protein A SUMO2 protein, human SUMO3 protein, human Small Ubiquitin-Related Modifier Proteins Ubiquitins DNA synthesome DNA-Directed DNA Polymerase Cysteine Endopeptidases SENP6 protein, human
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Dou Hong
Department of Cardiology, The University of Texas MD Anderson Cancer Center, The University of Texas Houston Health Science Center, Houston, TX 77030, USA.
Huang Chao
Singh Melissa
Carpenter Phillip B
Yeh Edward T H
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-4164
DOI
10.1016/j.molcel.2010.07.021
Published
2010-08-13
Pages
333-45
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC2928994
Subset
IM
Grants
NIAID NIH HHS · IR21AI076747-01 · United States
NIGMS NIH HHS · 2R56GM06581 · United States
NCI NIH HHS · R01 CA139520 · United States
NCI NIH HHS · CA 239520 · United States
NIAID NIH HHS · R21 AI076747 · United States
NCI NIH HHS · R01 CA139520-02 · United States
External Links
PubMed source DOI: 10.1016/j.molcel.2010.07.021 PMC Full Text View journal details
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