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PMID: 12093752 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

PA200, a nuclear proteasome activator involved in DNA repair.

The EMBO journal ·Vol. 21 ·No. 13 ·2002-07-01 ·Pages 3516-25

Ustrell V, Hoffman L, Pratt G, Rechsteiner M

Abstract

We have identified a novel 200 kDa nuclear protein that activates the proteasome. The protein, which we call PA200, has been purified to homogeneity from bovine testis and has been shown to activate proteasomal hydrolysis of peptides, but not proteins. Following gamma-irradiation of HeLa cells the uniform nuclear distribution of PA200 changes to a strikingly punctate pattern, a behavior characteristic of many DNA repair proteins. Homologs of PA200 are present in worms, plants and yeast. Others have shown that mutation of yeast PA200 results in hypersensitivity to bleomycin, and exposure of yeast to DNA damaging agents induces the PA200 message. Taken together, these findings implicate PA200 in DNA repair, possibly by recruiting proteasomes to double strand breaks.

MeSH Terms
Amino Acid Sequence Animals Cattle Cell Nucleus/chemistry Cysteine Endopeptidases/metabolism DNA Damage DNA Repair DNA, Complementary/genetics Enzyme Activation Gamma Rays HeLa Cells/enzymology,radiation effects Humans Male Mice Molecular Sequence Data Molecular Weight Multienzyme Complexes/metabolism Neoplasm Proteins/metabolism Nuclear Proteins/chemistry,isolation & purification,physiology Organ Specificity Peptides/metabolism Proteasome Endopeptidase Complex Protein Isoforms/chemistry,isolation & purification Rabbits Species Specificity Testis/chemistry
Chemicals
DNA, Complementary Multienzyme Complexes Neoplasm Proteins Nuclear Proteins Pa200 protein, mouse Peptides Protein Isoforms Cysteine Endopeptidases Proteasome Endopeptidase Complex
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Ustrell Vicença
Department of Biochemistry, University of Utah, 50 N Medical Drive, Salt Lake City, UT 84132, USA.
Hoffman Laura
Pratt Gregory
Rechsteiner Martin
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdf333
Published
2002-07-01
Pages
3516-25
Language
English
Region
England
NLM ID
8208664
PMCID
PMC126083
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/cdf333 PMC Full Text View journal details
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