Analysis of second-site mutations that suppress the multiple drug resistance phenotype of the yeast PDR1-7 allele.
The yeast PDR1 locus encodes a member of the C6 zinc cluster family of transcriptional regulatory proteins. Among the targets of PDR1 is the yeast PDR5 locus. The product of this gene is a member of the ATP-binding cassette (ABC) transmembrane protein family and plays a major role in inhibitor efflux. Mutations in PDR1 affect the relative level of PDR5 transcript and can therefore result in increased or decreased drug resistance. We isolated three second-site suppressors of a PDR1-7 semidominant hyper-resistant mutation. These mutants were drug hypersensitive, as compared with isogenic controls. Two of the three mutations contained alterations in a putative DNA-binding domain. Significantly, the mutant proteins exhibited reduced DNA-binding capacity.
McGuire
T M
TM
Department of Biology, Catholic University of America, Washington, DC 20064, USA.
Carvajal
E
E
Katzmann
D
D
Wagner
M
M
Moye-Rowley
W S
WS
Goffeau
A
A
Golin
J
J
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000483:Alleles; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018432:Drug Resistance, Multiple; D015966:Gene Expression Regulation, Fungal; D016153:Genes, Suppressor; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
D018528:ATP-Binding Cassette Transporters; D017931:DNA Primers; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; C085480:PDR1 protein, S cerevisiae; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors