The 19S regulatory complex of the proteasome functions independently of proteolysis in nucleotide excision repair

Mol Cell. 1999 Jun;3(6):687-95. doi: 10.1016/s1097-2765(01)80001-0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcysteine / analogs & derivatives
  • Acetylcysteine / pharmacology
  • Adenosine Triphosphatases / metabolism
  • Alkylation
  • Antibodies / pharmacology
  • Binding Sites
  • Cell Extracts
  • DNA Repair* / drug effects
  • DNA Repair* / radiation effects
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Fungal Proteins / chemistry
  • Fungal Proteins / genetics
  • Fungal Proteins / immunology
  • Fungal Proteins / metabolism*
  • Kinetics
  • Mutation
  • Peptide Hydrolases / chemistry
  • Peptide Hydrolases / genetics
  • Peptide Hydrolases / metabolism*
  • Precipitin Tests
  • Proteasome Endopeptidase Complex*
  • Protein Binding
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology
  • Repressor Proteins / metabolism
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / radiation effects
  • Saccharomyces cerevisiae Proteins*
  • Sequence Deletion
  • Ultraviolet Rays

Substances

  • Antibodies
  • Cell Extracts
  • DNA-Binding Proteins
  • Fungal Proteins
  • RAD23 protein, S cerevisiae
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • lactacystin
  • Peptide Hydrolases
  • Proteasome Endopeptidase Complex
  • ATP dependent 26S protease
  • Adenosine Triphosphatases
  • RPT4 protein, S cerevisiae
  • RPT6 protein, S cerevisiae
  • Acetylcysteine