The 26S proteasome negatively regulates the level of overall genomic nucleotide excision repair.
Regulation of protein expression can be achieved through destruction of proteins by the 26S: proteasome. Cellular processes that are regulated by proteolysis include cell cycle progression, stress responses and differentiation. Several nucleotide excision repair proteins in yeast and humans, such as Rad23, Rad4 and XPB, have been shown to co-purify with Cim3 and Cim5, AAA ATPases of the 19S: proteasome regulatory subunit. However, it has not been determined if nucleotide excision repair is regulated through protein destruction. We measured nucleotide excision repair in yeast mutants that are defective in proteasome function and found that the repair of the transcribed and non-transcribed strands of an RNA polymerase II-transcribed reporter gene was increased in the absence of proteasome function. Additionally, overexpression of the Rad4 repair protein, which is bound to the repair/proteolytic factor Rad23, conferred higher rates of nucleotide excision repair. Based on our data we suggest that a protein (or proteins) involved in nucleotide excision repair or in regulation of repair is degraded by the 26S proteasome. We propose that decreased proteasome function enables increased DNA repair, due to the transient accumulation of a specific repair factor, perhaps Rad4.
Lommel
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Laboratory for Cancer Research, College of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854-8020, USA.
Chen
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Madura
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Sweder
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K
D018736:DNA Adducts / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects; D004260:DNA Repair / Q000235:genetics*; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D016681:Genome, Fungal; D007700:Kinetics; D009154:Mutation / Q000235:genetics / Q000528:radiation effects; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011740:Pyrimidine Dimers / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D029702:Schizosaccharomyces pombe Proteins; D013696:Temperature; D014158:Transcription, Genetic / Q000235:genetics; D011503:Transglutaminases; D014466:Ultraviolet Rays; D015003:Yeasts / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development / Q000528:radiation effects
D018736:DNA Adducts; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D011740:Pyrimidine Dimers; C082463:RAD4 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D011503:Transglutaminases; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease