title: Using DNA damage sensitivity phenotypes to characterize mutations affecting proteasome function.
abstract: Most mutants affected either in the proteasome biogenesis or function accumulate polyubiquitylated proteins and display growth defects at 37°C or in the presence of canavanine, an arginine analog that impairs protein synthesis. We uncovered a new striking phenotype related to DNA damage for some proteasome mutants: mutant strains grew better than the wild type in the presence of specific genotoxic agents (4NQO, Cpt, and MMS). Hyperresistance to 4NQO or Cpt is a new sensitive tool to detect proteasomal defects. Here, we describe simple methods that can be used to show and quantitatively measure this phenotype in budding yeast.
authors.affiliation: CEA, iBiTecS, SBIGeM, Laboratoire du métabolisme de l'ADN et réponses aux génotoxiques, Gif-sur-Yvette, France.
authors.forename: Benoît Le
authors.initials: BL
authors.lastname: Tallec
authors.forename: Anne
authors.initials: A
authors.lastname: Peyroche
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology; D002166:Camptothecin / Q000494:pharmacology; D002172:Canavanine / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects*; D008741:Methyl Methanesulfonate; D009154:Mutation / Q000187:drug effects; D025821:Polyubiquitin; D046988:Proteasome Endopeptidase Complex / Q000235:genetics* / Q000378:metabolism*; D015363:Quinolones / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C120195:4-nitroquinolone-1-oxide; D015363:Quinolones; D029701:Saccharomyces cerevisiae Proteins; D025821:Polyubiquitin; D002172:Canavanine; D015112:4-Nitroquinoline-1-oxide; D008741:Methyl Methanesulfonate; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D002166:Camptothecin