title: RPD3 and ROM2 are required for multidrug resistance in Saccharomyces cerevisiae.
abstract: The PDR5 gene encodes the major multidrug resistance efflux pump in Saccharomyces cerevisiae. In drug-resistant cells, the hyperactive Pdr1p or Pdr3p transcriptional activators are responsible for the PDR5 upregulation. In this work, it is shown that the RPD3 gene encoding the histone deacetylase that functions as a transcriptional corepressor at many promoters and the ROM2 gene coding for the GDP/GTP exchange protein for Rho1p and Rho2p participating in signal transduction pathways are required for PDR5 transcription under cycloheximide-induced and noninduced conditions. Transposon insertion mutations in ROM2, RPD3 and some other genes encoding specific subunits of the large Rpd3L protein complex resulted in enhanced susceptibility of mutant cells to antifungals. In the rpd3 Delta and rom2 Delta mutants, the level of PDR5 mRNA and the rate of rhodamine 6G efflux were reduced. Unlike rpd3 Delta, in rom2 Delta mutant cells the drug hypersensitivity and the defect in PDR5 expression were suppressed by PDR1 or PDR3 overexpressed from heterologous promoters and by the hyperactive pdr3-9 mutant allele. The results indicate that Rpd3p histone deacetylase participating in chromatin remodeling and Rom2p participating in the cell integrity pathway are involved in the control of PDR5 expression and modulation of multidrug resistance in yeast.
authors.affiliation: Department of Microbiology and Virology, Faculty of Natural Sciences, Comenius University in Bratislava, Slovak Republic.
authors.forename: Silvia
authors.initials: S
authors.lastname: Borecka-Melkusova
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Kozovska
authors.forename: Imrich
authors.initials: I
authors.lastname: Hikkel
authors.forename: Vladimira
authors.initials: V
authors.lastname: Dzugasova
authors.forename: Julius
authors.initials: J
authors.lastname: Subik
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000935:Antifungal Agents / Q000494:pharmacology; D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins / Q000235:genetics; D026141:Drug Resistance, Multiple, Fungal; D015966:Gene Expression Regulation, Fungal; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000502:physiology*; D006655:Histone Deacetylases / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D012235:Rhodamines / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D018528:ATP-Binding Cassette Transporters; D000935:Antifungal Agents; D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; C089261:PDR3 protein, S cerevisiae; C092438:PDR5 protein, S cerevisiae; D012333:RNA, Messenger; C490929:ROM2 protein, S cerevisiae; D012235:Rhodamines; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C026188:rhodamine 6G; C071665:RPD3 protein, S cerevisiae; D006655:Histone Deacetylases