The transporters Pdr5p and Snq2p mediate diazaborine resistance and are under the control of the gain-of-function allele PDR1-12.

The spontaneous acquisition of resistance to a variety of unrelated cytotoxic compounds has important implications in medical treatment of infectious diseases and anticancer therapy. In the yeast Saccharomyces cerevisiae this phenomenon is caused by overexpression of membrane efflux pumps and is called pleiotropic drug resistance. We have found that allelic forms of the genes for the transcription activators Pdr1p and Pdr3p, designated PDR1-12 and PDR3-33, respectively, mediate resistance to diazaborine. Here we demonstrate that the transporters Pdr5p and Snq2p are involved in diazaborine detoxification. We report that in the PDR3-33 mutant diazaborine resistance is exerted mainly via overexpression of the PDR5 and SNQ2 genes, while in the PDR1-12 mutant, additional genes, i.e. the Yap1p target genes FLR1 and YCF1, are also involved in diazaborine detoxification. In addition, we show that in the presence of cycloheximide or diazaborine PDR5 can be activated by additional transcription factors beside Pdr1p and Pdr3p.