Transcriptional Control of Multidrug Resistance in the Yeast Saccharomyces

A major problem in chemotherapeutic treatment of many pathological conditions including cancer and fungal infections is the development of a multidrug-resistant state in the target cell. Saccharomyces cerevisiae cells can be isolated that have single genetic alterations that cause the resulting mutant strains to become tolerant of a wide range of compounds that would otherwise be toxic. These mutant cells are referred to as having a pleiotropic drug-resistant (Pdr) phenotype. Studies of these Pdr cells have demonstrated that mutations either within genes encoding transcriptional regulators or in their regulatory inputs lead to overexpression of downstream transporter proteins with associated multidrug resistance. This review is aimed at providing a framework for understanding the networks modulating expression of PDR genes in S. cerevisiae.