THE ATP-BINDING CASSETTE MULTIDRUG TRANSPORTER SNQ2 OF SACCHAROMYCES-CEREVISIAE - A NOVEL TARGET FOR THE TRANSCRIPTION FACTORS PDR1 AND PDR3

Pleiotropic drug resistance (PDR) in the yeast Saccharomyces cerevisia e can arise from overexpression of ATP-binding cassette (ABC) efflux p umps such as Pdr5 and Snq2. Mutations in the transcription factor gene s PDR1 and PDR3 are also associated with PDR. We show here that a pdr1 -3 mutant exhibits a PDR phenotype, including elevated resistance to t he mutagen 4-nitroquinoline-N-oxide, a known substrate for Snq2 but no t for Pdr5. Northern analysis and immunoblotting demonstrated that the SNQ2 gene is 10-fold overexpressed in a pdr1-3 gain-of-function mutan t strain, whereas Snq2 expression is severely reduced in a Delta pdr1 deletion strain, and almost abolished in a Delta pdr1 Delta pdr3 doubl e disruptant when compared to the PDR1 strain. However, expression of the Ste6 a-factor pheromone transporter, another yeast ABC transporter not associated with PDR, is unaffected in pdr1-3 mutant cells and in strains carrying Delta pdr1, Delta pdr3 or Delta pdr1 Delta pdr3 delet ions. Finally, DNA footprint analysis revealed that the SNQ2 promoter contains three binding sites for Pdr3. Our results identify SNQ2 as a novel target for both Pdr1 and Pdr3, and demonstrate that the PDR phen otype of a pdr1-3 mutant strain results from overexpression of more th an one ABC drug-efflux pump.