Yeast gene YRR1, which is required for resistance to 4-nitroquinoline N-oxide, mediates transcriptional activation of the multidrug resistance transporter gene SNQ2.
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.
Cui
Z
Z
Department of Molecular Biotechnology, Faculty of Engineering, Hiroshima University, Higashi-Hiroshima, Japan.
Shiraki
T
T
Hirata
D
D
Miyakawa
T
T
D015112:4-Nitroquinoline-1-oxide / Q000378:metabolism / Q000494:pharmacology*; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000595:Amino Acid Sequence; D015152:Blotting, Northern; D003001:Cloning, Molecular; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics* / Q000502:physiology; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005800:Genes, Fungal / Q000235:genetics; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009153:Mutagens / Q000378:metabolism / Q000494:pharmacology; D010641:Phenotype; D011714:Pyrans / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013141:Spiro Compounds / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects; D016335:Zinc Fingers / Q000235:genetics
D018528:ATP-Binding Cassette Transporters; D005656:Fungal Proteins; D009153:Mutagens; D011714:Pyrans; C101797:SNQ2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D013141:Spiro Compounds; D015534:Trans-Activators; C068098:reveromycin A; D015112:4-Nitroquinoline-1-oxide