Yeast gene YRR1, which is required for resistance to 4-nitroquinoline N-oxide, mediates transcriptional activation of the multidrug resistance transporter gene SNQ2

Mol Microbiol. 1998 Sep;29(5):1307-15. doi: 10.1046/j.1365-2958.1998.01027.x.


We have cloned and characterized a Saccharomyces cerevisiae gene YRR1 that is important for resistance to the mutagen 4-nitroquinoline N-oxide (4-NQO). The wild-type YRR1 gene encodes a protein that contains a Zn(II)2Cys6-type zinc-finger motif. Disruption of the YRR1 gene leads to hypersensitivity to 4-NQO. A dominant mutation (YRR1-1) that confers strong resistance to 4-NQO has been identified. Epistasis analysis demonstrated that 4-NQO resistances mediated by the YRR1 and YRR1-1 alleles require the presence of the SNQ2 gene that encodes a multidrug resistance ATP binding cassette superfamily protein responsible for 4-NQO export. Northern blot analysis of SNQ2 mRNA levels indicated that Yrr1p is involved in basal and drug-induced transcriptional activation of SNQ2, whereas Pdr1p/Pdr3p transcription factors are mainly involved in basal SNQ2 expression. In the YRR1-1 mutant, the level of SNQ2 mRNA is constitutively elevated. These results establish that Yrr1p is important for 4-NQO resistance by mediating transcriptional activation of the SNQ2 gene in response to the stress imposed by 4-NQO. The gain-of-function mutation of Yrr1-1p was attributable to the duplication of a 12-amino-acid sequence generated near the carboxy terminus.

MeSH terms

  • 4-Nitroquinoline-1-oxide / metabolism
  • 4-Nitroquinoline-1-oxide / pharmacology*
  • ATP-Binding Cassette Transporters / genetics*
  • Amino Acid Sequence
  • Blotting, Northern
  • Cloning, Molecular
  • Drug Resistance, Microbial
  • Drug Resistance, Multiple / genetics*
  • Fungal Proteins / genetics*
  • Fungal Proteins / physiology
  • Gene Expression Regulation, Fungal / drug effects
  • Genes, Fungal / genetics
  • Molecular Sequence Data
  • Mutagenesis, Insertional
  • Mutagens / metabolism
  • Mutagens / pharmacology
  • Phenotype
  • Pyrans / metabolism
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Spiro Compounds / metabolism
  • Trans-Activators / genetics*
  • Trans-Activators / physiology
  • Transcriptional Activation* / drug effects
  • Zinc Fingers / genetics


  • ATP-Binding Cassette Transporters
  • Fungal Proteins
  • Mutagens
  • Pyrans
  • SNQ2 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Spiro Compounds
  • Trans-Activators
  • reveromycin A
  • 4-Nitroquinoline-1-oxide