The significance of the role of the YAP gene family in adaptation and tolerance to HMF is confirmed by growth responses of the deletion mutations. Single YAP gene deletion mutations were able to grow normally without HMF treatment. However, in the selleck chemicals llc presence of 15 mM HMF, mutations yap1, yap4, p5, and yap6 showed delayed growth compared with their parental strain. Among these, yap1 displayed a 4 day long lag phase, indicating a profound functional defect affected by the YAP1 gene. PDR family and PDR1 3 involved regulatory interactions Among the significantly induced genes by HMF, at least 15 genes were categorized into the PDR family. Many genes displayed consistent induced expressions ranging from 3 to 30 fold increases during the lag phase.

Gene products of these increased tran scripts were in the protein categories of drug toxin transport for TPO1 and TPO4, Transport ATPase for RSB1, and ABC transporters for PDR15. SNQ2, YOR1, PDR5, and PDR12 encoding proteins shared functions of all these three categories. In addi tion, many PDR proteins have functions such as ATP binding and chemical agent resistance. Most of these genes have the pleiotropic drug response ele ment in their promoter regions. HMF induced transcription factor genes PDR1 and PDR3 regulate gene expression under a large variety of unrelated chemical stress conditions by binding to the PDRE of target genes. Both Pdr1p and Pdr3p recognize CGG triplets oriented in opposite directions to form an inverted repeat, and able to form homodimers or heterodimers to activate target gene expression.

Many induced genes regulated by Pdr1p and or Pdr3p in this group are involved in export of both xenobiotic compounds and endogenous toxic metabolites using ATP binding cassette transpor ters, lipid composi tion of the plasma membrane, export of polyamines by polyamine transporters, DNA repairing, and other functions. At least eight genes induced by HMF in this study were regulated by both Pdr1p and Pdr3p. Pdr1p and Pdr3p also recognize and activate other subsets of genes. Pdr3p participates in certain processes that do not involve Pdr1p, such as reg ulating DNA damage inducible genes MAG1 and DDI1. Similarly, some genes are only regulated by Pdr1p, such as RSB1, ADH7, and PRE3. We also found that the PDR3 promoter contains two PDREs that can be autoregulated by itself in addition to being a reg ulon of Pdr1p. PDR1 and PDR3 also demon strated regulatory connections with a broad range of functional GSK-3 category genes as well as most active regula tory genes. PDR 1 and PDR3 gene deletion mutations were assayed to confirm their influence on the expression of the potential regulons.