Document Detail


Crystal structure of SUMO-modified proliferating cell nuclear antigen.
MedLine Citation:
PMID:  21167178     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Eukaryotic proliferating cell nuclear antigen (PCNA) is a replication accessory protein that functions in DNA replication, repair, and recombination. The various functions of PCNA are regulated by posttranslational modifications including mono-ubiquitylation, which promotes translesion synthesis, and sumoylation, which inhibits recombination. To understand how SUMO modification regulates PCNA, we generated a split SUMO-modified PCNA protein and showed that it supports cell viability and stimulates DNA polymerase δ activity. We then determined its X-ray crystal structure and found that SUMO occupies a position on the back face of the PCNA ring, which is distinct from the position occupied by ubiquitin in the structure of ubiquitin-modified PCNA. We propose that the back of PCNA has evolved to be a site of regulation that can be easily modified without disrupting ongoing reactions on the front of PCNA, such as normal DNA replication. Moreover, these modifications likely allow PCNA to function as a tool belt, whereby proteins can be recruited to the replication machinery via the back of PCNA and be held in reserve until needed.
Authors:
Bret D Freudenthal; John E Brogie; Lokesh Gakhar; Christine M Kondratick; M Todd Washington
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-12-15
Journal Detail:
Title:  Journal of molecular biology     Volume:  406     ISSN:  1089-8638     ISO Abbreviation:  J. Mol. Biol.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-28     Completed Date:  2011-03-14     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  2985088R     Medline TA:  J Mol Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  9-17     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Biochemistry, University of Iowa College of Medicine, Iowa City, IA 52242-1109, USA.
Data Bank Information
Bank Name/Acc. No.:
PDB/3PGE
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MeSH Terms
Descriptor/Qualifier:
Antigens, Nuclear / chemistry*,  genetics,  metabolism
Cell Survival
Crystallography, X-Ray
DNA Polymerase III / analysis
Proliferating Cell Nuclear Antigen
Protein Conformation
Saccharomyces cerevisiae / metabolism*
Saccharomyces cerevisiae Proteins / chemistry*,  genetics,  metabolism
Small Ubiquitin-Related Modifier Proteins / chemistry*,  metabolism
Sumoylation*
Grant Support
ID/Acronym/Agency:
R01 GM081433-03/GM/NIGMS NIH HHS; R01GM081433/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, Nuclear; 0/POL30 protein, S cerevisiae; 0/Proliferating Cell Nuclear Antigen; 0/Saccharomyces cerevisiae Proteins; 0/Small Ubiquitin-Related Modifier Proteins; EC 2.7.7.-/DNA Polymerase III
Comments/Corrections

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