Analysis of second-site mutations that suppress the multiple drug resistance phenotype of the yeast PDR1-7 allele

Gene. 1995 Dec 29;167(1-2):151-5. doi: 10.1016/0378-1119(95)00663-x.

Abstract

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.

Publication types

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

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Alleles
  • Base Sequence
  • DNA Primers / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Drug Resistance, Multiple*
  • Gene Expression Regulation, Fungal
  • Genes, Suppressor
  • Macromolecular Substances
  • Molecular Sequence Data
  • RNA, Messenger / genetics
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators*
  • Transcription Factors / genetics*
  • Transcription, Genetic

Substances

  • ATP-Binding Cassette Transporters
  • DNA Primers
  • DNA-Binding Proteins
  • Macromolecular Substances
  • PDR1 protein, S cerevisiae
  • RNA, Messenger
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • Transcription Factors