Regulation of Purine Nucleotide Biosynthesis in Yeast

Georgetown University, Washington DC

Investigators

Abstract

Cells must adapt to the changing conditions in their environment by sensing external conditions and signaling these conditions to alter expression of genes whose products permit growth or survival under the new conditions. In general, transcription factors are the recipients of the signals and their activity is increased or decreased dependent upon conditions. Transcription factors, in turn, bind to specific DNA sites and recruit components of the transcriptional machinery including the general transcription factors, coactivators, chromatin remodeling complexes and RNA polymerase II. Frequently, gene expression depends upon multiple activators functioning in a combinatorial manner to specifically stimulate transcription. The ADE genes of the yeast Saccharomyces cerevisiae are a system the principal investigator has been studying to determine how a purine limitation signal is detected and transmitted to the activators Bas1 and Bas2. Expression of the ADE genes is inherently combinatorial as both activators are required. However, the individual roles that these factors play in activation function are unknown. In this project, the roles that the activators Bas1 and Bas2 play during transcription of the ADE genes and how they receive the intracellular regulatory signal will be studied to understand the underlying mechanisms that permit these activators to respond to a purine limitation signal and to promote transcription. While the focus of this research is on ADE gene regulation by Bas1 and Bas2, these studies will add to our understanding of combinatorial mechanisms for transcription regulation as well as providing insights into adenylate regulation in eukaryotes. The research conducted by the principal investigator has provided training opportunities to a large number of undergraduate, graduate and post-doctoral trainees, and will continue to do so through this project.