PDR1 and PDR3 encode transcriptional regulatory proteins that control the expression of proteins that act directly to confer the Pdr phenotype. Genetic experiments demonstrated that a strain lacking PDR1 is drug sensitive but a strain lacking PDR3 still has normal drug resistance. Recent work has uncovered a gene called PDR13 that stimulates the action of Pdr1p, but not Pdr3p, during the response to drug challenge. PDR13 encodes an Hsp70 protein. Current efforts focus on understanding how Pdr13p influences drug resistance and regulates Pdr1p activity.
Free radicals are important agents of cellular damage.
We are studying oxidative stress resistance in S. cerevisiae as a simple model for resistance to oxidant damage in eukaryotic cells. Specifically, we are analyzing the structure and function of the transcription factor yAP-1. This protein is a member of the bZip family of transcriptional regulatory proteins and exhibits an enhanced ability to activate expression of target genes after cells are exposed to oxidants. We have carried out domain mapping experiments on this regulatory protein and defined several different segments of the factor that are required for the oxidative stress response of yAP-1. We have also identified several target genes under yAP-1 control that allow this factor to exert its effect over oxidative stress tolerance.