The 19S regulatory complex of the proteasome functions independently of proteolysis in nucleotide excision repair.
The 26S proteasome degrades proteins targeted by the ubiquitin pathway, a function thought to explain its role in cellular processes. The proteasome interacts with the ubiquitin-like N terminus of Rad23, a nucleotide excision repair (NER) protein, in Saccharomyces cerevisiae. Deletion of the ubiquitin-like domain causes UV radiation sensitivity. Here, we show that the ubiquitin-like domain of Rad23 is required for optimal activity of an in vitro NER system. Inhibition of proteasomal ATPases diminishes NER activity in vitro and increases UV sensitivity in vivo. Surprisingly, blockage of protein degradation by the proteasome has no effect on the efficiency of NER. This establishes that the regulatory complex of the proteasome has a function independent of protein degradation.
Department of Medicine and Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235, USA.
S J
SJ
Russell
S H
SH
Reed
W
W
Huang
E C
EC
Friedberg
S A
SA
Johnston
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000478:Alkylation; D000906:Antibodies / Q000494:pharmacology; D001665:Binding Sites; D002457:Cell Extracts; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007700:Kinetics; D009154:Mutation; D010447:Peptide Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011233:Precipitin Tests; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology* / Q000235:genetics / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins; D017384:Sequence Deletion; D014466:Ultraviolet Rays
D000906:Antibodies; D002457:Cell Extracts; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C490846:RAD23 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C067713:lactacystin; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D000251:Adenosine Triphosphatases; C103015:RPT4 protein, S cerevisiae; C069670:RPT6 protein, S cerevisiae; D000111:Acetylcysteine