PDR3, A NEW YEAST REGULATORY GENE, IS HOMOLOGOUS TO PDR1 AND CONTROLSTHE MULTIDRUG-RESISTANCE PHENOMENON

The Saccharomyces cerevisiae PDR3 gene, located near the centromere of chromosome II, has been completely sequenced and characterised. Mutat ions pdr3-1 and pdr3-2, which confer resistance to several antibiotics can be complemented by a wild-type allele of the PDR3 gene. The seque nce of the wild-type PDR3 gene revealed the presence of a long open re ading frame capable of encoding a 976-amino acid protein. The protein contains a single Zn(II)(2)Cys(6) binuclear-type zinc finger homologou s to the DNA-binding motifs of other transcriptional activators from l ower eukaryotes. Evidence that the PDR3 protein is a transcriptional a ctivator was provided by demonstrating that DNA-bound LexA-PDR3 fusion proteins stimulate expression of a nearby promoter containing LexA bi nding sites. The use of LexA-PDR3 fusions revealed that the protein co ntains two activation domains, one localised near the N-terminal, cyst eine-rich domain and the other localised at the C-terminus. The salien t feature of the PDR3 protein is its similarity to the protein coded b y PDR1, a gene responsible for pleiotropic drug resistance. The two pr oteins show 36% amino acid identity over their entire length and their zinc finger DNA-binding domains are highly conserved. The fact that t he absence of both PDR1 and PDR3 (simultaneous disruption of the two g enes) enhances multidrug sensitivity strongly suggests that the two tr anscriptional factors have closely related functions.