The goal of this research is to gain insight into the process of starvation-induced growth arrest in the yeast Saccharomyces cerevisiae. Although growth arrest is a universal response to starvation, the process by which it occurs and the relationship between growth arrest and the characteristic physiological changes associated with the arrest are not well understood. Recently several genes have been identified whose transcripts exhibit distinct patterns of accumulation as cells undergo starvation-induced arrest. The accumulation of these transcripts in arrest-defective mutants will be studied to determine the time at which the mutants stop development and, thus, to map control points during arrest. The promoter of one gene whose arrest- specific transcript accumulation is cAMP-mediated will be fused to a selectable marker gene to isolate regulatory mutants. Mutants obtained by this selection will be analyzed to determine whether similarly-regulated genes are essential, whether their expression is sufficient to induce arrest, and whether cAMP is directly involved in this regulation. Nutrient limitation is one of the most common stresses affecting cell viability and growth. Because of this, there is great selective pressure for cells to sense, respond to, and survive prolonged periods of starvation. When faced with nutrient limitations, yeast, like many other organisms, ceases dividing and undergoes a series of characteristic morphological, biochemical, and physiological changes. The proposed research will provide insight into the mechanism of starvation induced growth arrest by characterizing some of the genes whose expression is altered during nutrient limitation. Because starvation is a universal stress, understanding the general mechanisms by which simple eucaryotic organisms, like yeast, respond to and survive starvation may well provide insight into these mechanisms in higher organisms.
