The ability to regulate growth and division is recognized as one of the most important characteristics of living cells. However, in nature cells spend most of their time in a quiescent state or stationary phase, during which pathways that regulate non-growing, non-dividing cells become critical. Because most of a cell's life may be spent in a quiescent state, the ability to regulate entry into, survival during, and exit from this state is as important for species survival as the ability to divide. Although the quiescent state is of obvious significance, little is known about the mechanisms that allow cells to enter or exit this state or to survive for long periods of time, experiencing a variety of life-threatening stresses, including starvation. The long-term objective of this is to understand the molecular events that are important for the process of entry into, survival during, and exit from stationary phase, the quiescent state, in the yeast Saccharomyces cerevisiae. In prior research two novel genes, SNZ1 (SNooZe) and SNO1 (SNZ-proximal Open reading frame) that are induced in stationary phase were identified. SNZ and SNO genes are members of highly conserved gene families that are found in divergently transcribed pairs. Most yeast strains contain three SNZ/SNO gene pairs. Snz proteins are the most highly conserved proteins yet identified that are present in all three phylogenetic domains, i.e. the archaea, bacteria, and eucarya. The majority of this project focuses on SNZ1. In addition to its induction in stationary phase, SNZ1 is induced by specific amino acid, purine, and pyrimidine starvation. snzl mutants are also exquisitely sensitive to 6 azauracil, an inhibitor of the UTP and GTP biosynthetic pathways, and this sensitivity is suppressed by addition of uracil. These results suggest that Snzl protein, and probably also Sno 1 protein, is required for production of pyrimidine nucleotides, possibly through regulation of or involvement in a salvage pathway required in yeast during times of dire starvation.
