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PMID: 12420141 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Proteolysis of a nucleotide excision repair protein by the 26 S proteasome.

Current genetics ·Vol. 42 ·No. 1 ·2002-10-00 ·Pages 9-20

Lommel L, Ortolan T, Chen L, Madura K, Sweder KS

Abstract

The 26 S proteasome degrades a broad spectrum of proteins and interacts with several nucleotide excision repair (NER) proteins, including the complex of Rad4 and Rad23 that binds preferentially to UV-damaged DNA. The rate of NER is increased in yeast strains with mutations in genes encoding subunits of the 26 S proteasome, indicating that it could negatively regulate a repair process. The specific function of the 26 S proteasome in DNA repair is unclear. It might degrade DNA repair proteins after repair is completed or act as a molecular chaperone to promote the assembly or disassembly of the repair complex. In this study, we show that Rad4 is ubiquitylated and that Rad23 can control this process. We also find that ubiquitylated Rad4 is degraded by the 26 S proteasome. However, the interaction of Rad23 with Rad4 is not only to control degradation of Rad4, but also to assist in assembling the NER incision complex at UV-induced cyclobutane pyrimidine dimers. We speculate that, following the completion of DNA repair, specific repair proteins might be degraded by the proteasome to regulate repair.

MeSH Terms
DNA Ligases/biosynthesis,genetics,metabolism DNA Repair/physiology DNA-Binding Proteins/metabolism Fungal Proteins/metabolism Mutation Peptide Hydrolases/genetics,metabolism Proteasome Endopeptidase Complex Saccharomyces cerevisiae/physiology Saccharomyces cerevisiae Proteins Ubiquitin/metabolism Ultraviolet Rays
Chemicals
DNA-Binding Proteins Fungal Proteins RAD23 protein, S cerevisiae Saccharomyces cerevisiae Proteins Ubiquitin Peptide Hydrolases Proteasome Endopeptidase Complex ATP dependent 26S protease DNA Ligases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Lommel Lori
Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway 08854-8020, USA.
Ortolan Tatiana
Chen Li
Madura Kiran
Sweder Kevin S
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Article Info
Journal
Current genetics
Abbr.
Curr Genet
ISSN
0172-8083
DOI
10.1007/s00294-002-0332-9
Published
2002-10-00
Epub
2002-00-11
Pages
9-20
Language
English
Region
United States
NLM ID
8004904
Subset
IM
Grants
NCI NIH HHS · 1R01 CA83875 · United States
External Links
PubMed source DOI: 10.1007/s00294-002-0332-9 View journal details
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