| Summary: | In <i>Saccharomyces</i><i>cerevisiae</i>, the Rpd3L complex contains a histone deacetylase, Rpd3, and the DNA binding proteins, Ume6 and Ash1, and acts as a transcriptional repressor or activator. We previously showed that <i>RPD3</i> and <i>UME6</i> are required for the activation of <i>PDR5</i>, which encodes a major efflux pump, and pleiotropic drug resistance (PDR) in ρ<sup>0/−</sup> cells, which lack mitochondrial DNA. However, there are inconsistent reports regarding whether <i>RPD3</i> and <i>UME6</i> are required for Pdr5-mediated PDR in ρ<sup>+</sup> cells with mitochondrial DNA. Since <i>PDR5</i> expression or PDR in the ρ<sup>+</sup> cells of the <i>rpd3</i>Δ and <i>ume6</i>Δ mutants have primarily been examined using fermentable media, mixed cultures of ρ<sup>+</sup> and ρ<sup>0/−</sup> cells could be used. Therefore, we examined whether <i>RPD3</i> and <i>UME6</i> are required for basal and drug-induced <i>PDR5</i> transcription and PDR in ρ<sup>+</sup> cells using fermentable and nonfermentable media. <i>UME6</i> suppresses the basal transcription levels of the ABC transporters, including <i>PDR5</i>, and drug resistance in ρ<sup>+</sup> cells independent of the carbon source used in the growth medium. In contrast, <i>RPD3</i> is required for drug resistance but did not interfere with the basal <i>PDR5</i> mRNA levels. <i>UME6</i> is also required for the cycloheximide-induced transcription of <i>PDR5</i> in nonfermentable media but not in fermentable media.
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