A Dominant Allele of PDR1 Alters Transition Metal Resistance in Yeast

Abstract

A yeast mutant was found to have defective growth on low iron medium despite a normal high affinity iron transport system. The phenotype results from a gain of function mutation in PDR1, which encodes a transcription factor that acts as a regulator of pleiotropic drug resistance in Saccharomyces cerevisiae. The mutant allele, PDR1(R821H), was found to result in increased expression of at least 19 genes, three of which are ATP-binding cassette (ABC) transporters. Expression of at least six genes was required to show the low iron growth defect. Wild type cells transformed with the PDR1(R821H) allele or a PDR1 dominant allele (PDR1-3) showed the low iron growth defect as well as increased resistance to drugs such as cycloheximide and oligomycin. Transformation of PDR1(R821H) into Deltaccc1 cells, which were previously shown to have increased sensitivity to high iron medium because of defective vacuolar iron storage (Li, L., Chen, O. S., Ward, D. M., and Kaplan, J. (2001) J. Biol. Chem. 276, 29515-29519), conferred resistance to high iron medium. Cells expressing PDR1(R821H) also showed increased resistance to copper and manganese because of increased metal export. These results suggest that expression of PDR1-regulated genes affects both efflux and storage of transition metals.