title: PDR2 Gain-of-function mutations eliminate the need for Pdr1 and require the UBP6 product for resistance to translational inhibitors.
abstract: The yeast YRR1 gene was identified as a sequence encoding a protein that is related in structure to the Pdr1 and Pdr3 zinc cluster transcription factors. Dominant gain-of-function mutations were recovered that cause a multidrug resistance to inhibitors transported by the SNQ2 and YOR1 proteins. It was previously reported by others that null mutations in YRR1 cause hypersensitivity to these agents. In this study, evidence is presented for allelism between YRR1 and a previously identified locus: PDR2. Further characterization of hyperresistant PDR2 alleles and the initial characterization of a loss-of-function mutation created by a Tn3 insertion are described. Surprisingly, the PDR2-2-mediated hyperresistance to chloramphenicol, anisomycin, and cycloheximide requires the function of the UBP6 gene and at least one other gene product. The PDR2-2 allele eliminates the requirement for Pdr1 although, in our genetic backgrounds, elimination of Pdr2 function has little or no phenotypic effect.
authors.affiliation: Department of Biology, The Catholic University of America, Washington, DC 20064, USA.
authors.forename: James
authors.initials: J
authors.lastname: Keeven
authors.forename: Daejin
authors.initials: D
authors.lastname: Ko
authors.forename: Joshua
authors.initials: J
authors.lastname: Shallom
authors.forename: Beth
authors.initials: B
authors.lastname: Uccelini
authors.forename: John
authors.initials: J
authors.lastname: Golin
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000841:Anisomycin / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology; D001483:Base Sequence; D002701:Chloramphenicol / Q000494:pharmacology; D004271:DNA, Fungal; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D026141:Drug Resistance, Multiple, Fungal / Q000235:genetics*; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029701:Saccharomyces cerevisiae Proteins; D017422:Sequence Analysis, DNA; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors
chemical_list: D018528:ATP-Binding Cassette Transporters; D000935:Antifungal Agents; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D008565:Membrane Proteins; C085480:PDR1 protein, S cerevisiae; C092438:PDR5 protein, S cerevisiae; D011500:Protein Synthesis Inhibitors; C101797:SNQ2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C097077:YOR1 protein, S cerevisiae; D002701:Chloramphenicol; D000841:Anisomycin; D010450:Endopeptidases; C109028:UBP6 protein, S cerevisiae