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J. Biol. Chem., Vol. 277, Issue 20, 17671-17676, May 17, 2002

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Zinc Cluster Protein Rdr1p Is a Transcriptional Repressor of the PDR5 Gene Encoding a Multidrug Transporter^*

Karen Hellauer, Bassel Akache, Sarah MacPherson^§, Edith Sirard, and Bernard Turcotte^§¶

From the Departments of  Medicine, ^¶ Biochemistry, and ^§ Microbiology and Immunology, McGill University Health Centre, Royal Victoria Hospital, McGill University, 687 Pine Ave. West, Montréal, Québec H3A 1A1, Canada

The yeast PDR5 gene encodes an efflux pump that confers multidrug resistance. Expression of PDR5 is positively regulated by the transcription factors Pdr1p and Pdr3p that recognize the same pleiotropic drug resistance elements (PDREs) in the PDR5 promoter. Pdr1p and Pdr3p belong to the Gal4p family of zinc cluster proteins. The function of RDR1 (YOR380W), which also encodes a member of this family, is unknown. To identify target genes for Rdr1p, we have performed whole-genome analysis of gene expression with DNA microarrays. Our results show that Rdr1p is a transcriptional repressor of five genes, including PDR5. A rdr1 strain has increased resistance to cycloheximide, as expected from the overexpression of PDR5. In addition, the activity of a PDR5-lacZ reporter is increased in a rdr1 strain. All (but one) genes affected by removal of Rdr1p contain PDREs in their promoters. We tested if the effect of Rdr1p is mediated through PDREs by inserting this DNA element in front of a minimal promoter. Activity of this reporter was increased in a rdr1 strain. Moreover, mutations known to reduce binding of Pdr1/Pdr3p abolished the induction observed in the rdr1 strain. Thus, we have identified a transcriptional repressor involved in the control of multidrug resistance.

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