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Interplay among regulators of multidrug resistance in Kluyveromyces lactis.

The KlYAP1 and KlPDR1 genes encode two main transcriptional regulators involved in the control of multidrug resistance in Kluyveromyces lactis. Deletion of KlPDR1 or KlYAP1 genes in K. lactis generated strain hypersusceptible to diamide, benomyl, fluconazole and oligomycin. Overexpression of genes KlPDR1 or KlYAP1 from a multicopy plasmid in the Klpdr1Δ mutant strain increased the tolerance of transformants to all the drugs tested. YRE response elements were found in the promoter of the KlPDR1 gene. Gel retardation assays confirmed the binding of KlYap1p to the YREs in the KlPDR1 gene promoter indicating that KlYap1p can control the KlPDR1 gene expression.