Document Detail


Rap80 protein recruitment to DNA double-strand breaks requires binding to both small ubiquitin-like modifier (SUMO) and ubiquitin conjugates.
MedLine Citation:
PMID:  22689573     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ubiquitin (Ub) modifications at sites of DNA double-strand breaks (DSBs) play critical roles in the assembly of signaling and repair proteins. The Ub-interacting motif (UIM) domain of Rap80, which is a component of the BRCA1-A complex, interacts with Ub Lys-63 linkage conjugates and mediates the recruitment of BRCA1 to DSBs. Small ubiquitin-like modifier (SUMO) conjugation also occurs at DSBs and promotes Ub-dependent recruitment of BRCA1, but its molecular basis is not clear. In this study, we identified that Rap80 possesses a SUMO-interacting motif (SIM), capable of binding specifically to SUMO2/3 conjugates, and forms a tandem SIM-UIM-UIM motif at its N terminus. The SIM-UIM-UIM motif binds to both Ub Lys-63 linkage and SUMO2 conjugates. Both the SIM and UIM domains are required for efficient recruitment of Rap80 to DSBs immediately after damage and confer cellular resistance to ionizing radiation. These findings propose a model in which SUMO and Ub modification is coordinated to recruit Rap80 and BRCA1 to DNA damage sites.
Authors:
Xin Hu; Atanu Paul; Bin Wang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-06-11
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-23     Completed Date:  2012-10-18     Revised Date:  2013-07-23    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  25510-9     Citation Subset:  IM    
Affiliation:
Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Motifs
Animals
BRCA1 Protein / genetics,  metabolism*
Carrier Proteins / genetics,  metabolism*
Cell Cycle Proteins / genetics,  metabolism*
DNA Breaks, Double-Stranded*
Humans
Mice
Models, Biological*
Nuclear Proteins / genetics,  metabolism*
Protein Structure, Tertiary
Small Ubiquitin-Related Modifier Proteins / genetics,  metabolism*
Sumoylation*
Transcription Factors / genetics,  metabolism*
Ubiquitins / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
CA155025/CA/NCI NIH HHS; R01 CA155025/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/BRCA1 Protein; 0/BRCA1 protein, human; 0/Carrier Proteins; 0/Cell Cycle Proteins; 0/Nuclear Proteins; 0/RAP80 protein, human; 0/Rap80 protein, mouse; 0/SUMO2 protein, human; 0/SUMO2 protein, mouse; 0/SUMO3 protein, human; 0/Small Ubiquitin-Related Modifier Proteins; 0/Sumo3 protein, mouse; 0/Transcription Factors; 0/Ubiquitins
Comments/Corrections

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