PDR5, A NOVEL YEAST MULTIDRUG-RESISTANCE CONFERRING TRANSPORTER CONTROLLED BY THE TRANSCRIPTION REGULATOR PDR1

The complete sequence of the pleiotropic drug resistance gene PDR5 fro m Saccharomyces cerevisiae is reported and analyzed. PDR5 encodes a 16 0-kDa protein with a predicted duplicated six membrane-span domain and a repeated putative ATP-binding domain. PDR5 shares this structural f eature with the mammalian multidrug resistance pumps as well as the fu nctional capacity of conferring resistance to various inhibitors upon amplification (Leppert, G., McDevitt, R., Falco, S. C., Van Dyk, T. K. , Ficke, M. B., and Golin, J. (1990) Genetics 125, 13-20). The yeast P DR5 is thus a new member of the ABC (ATP-binding cassette) protein sup erfamily. Mutations in another yeast pleiotropic drug resistance gene, PDR1, encoding a putative transcription regulator (Balzi, E., Chen, W ., Ulaszewski, S., Capieaux, E., and Goffeau, A. (1987) J. Biol. Chem. 262, 16871-16879), increase markedly the mRNA levels of the PDR5 and STE6 genes. The multidrug resistance mutations pdr1-3 and pdr1-6 also lead to considerable overexpression of the PDR5 plasma membrane protei n.