PDR3, a new yeast regulatory gene, is homologous to PDR1 and controls the multidrug resistance phenomenon

• Published in: Molecular & general genetics Vol. 244; no. 5; p. 501
• Main Authors: Delaveau, T. (Centre National de la Reserche Scientifique URA. Ecole Normale Superieure, Paris (France). Lab. de Genetique Moleculaire), Delahodde, A, Carvajal, E, Subik, J, Jacq, C
• Format: Journal Article
• Language: English
• Published: Germany 01.09.1994
• Subjects: ADN; Amino Acid Sequence; Base Sequence; Chromosomes, Fungal; CINC; DNA, Fungal - genetics; DNA-Binding Proteins - genetics; Drug Resistance, Microbial - genetics; GENE; Gene Expression Regulation, Fungal; GENES; Genes, Fungal; Genes, Regulator; Microbial Sensitivity Tests; Molecular Sequence Data; Multidrug resistance; Open Reading Frames; Recombinant Fusion Proteins; RESISTANCE AUX PRODUITS CHIMIQUES; RESISTENCIA QUIMICA; Restriction Mapping; SACCHAROMYCES CEREVISIAE; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins; Sequence Alignment; Sequence Homology, Nucleic Acid; Transcription factor; Transcription Factors - genetics; ZINC; Zinc finger; Zinc Fingers
• ISSN: 0026-8925; 1432-1874
• DOI: 10.1007/BF00583901

The Saccharomyces cerevisiae PDR3 gene, located near the centromere of chromosome 2, has been completely sequenced and characterised. Mutations pdr3-1 and pdr3-2, which confer resistance to several antibiotics can be complemented by a wild-type allele of the PDR3 gene. The sequence of the wild-type PDR3 gene revealed the presence of a long open reading frame capable of encoding a 976-amino acid protein. The protein contains a single Zn(2)(2)Cys(6) binuclear-type zinc finger homologous to the DNA-binding motifs of other transcriptional activators from lower eukaryotes. Evidence that the PDR3 protein is a transcriptional activator was provided by demonstrating that DNA-bound LexA-PDR3 fusion proteins stimulate expression of a nearby promoter containing LexA binding sites. The use of LexA-PDR3 fusions revealed that the protein contains two activation domains, one localised near the N-terminal, cysteine-rich domain and the other localised at the C-terminus. The salient feature of the PDR3 protein is its similarity to the protein coded by PDR1, a gene responsible for pleiotropic drug resistance. The two proteins show 36% amino acid identity over their entire length and their zinc finger DNA-binding domains are highly conserved. The fact that the absence of both PDR1 and PDR3 (simultaneous disruption of the two genes) enhances multidrug sensitivity strongly suggests that the two transcriptional factors have closely related functions.