The role of the nutrients in G1 phase progression of Saccharomyces cerevisiae

Abstract

Organisms that have optimally integrated fast reproduction with high survival have a strategic advantage over less adapted species during evolution. This thesis focusses on the main decision point in the life cycle of the yeast Saccharomyces cerevisiae, at which the cell decides to rapidly grow and devide or accumulate reserve carbohydrates and delay cell cycle progression. This main decision point is located at the end of the G1 phase of the cell cycle and is called ‘Start’. The decision to pass Start depends on environmental conditions, like the nutrient supply. By growing cells of S. cerevisiae at different growth rates, it was shown that activation of the MAP kinase protein Slt2 (Mpk1) is one of the key regulators of progression through the cell cycle in response to the nutrient supply. Overexpression and deletion studies confirmed the requirement of phosphorylated Slt2 for fast progression past the decision point Start. As the cell cycle is elongated, cells accumulate the intracellular carbohydrates trehalose and glycogen during the G1 phase. By using nitrogen-limited continuous cultures, it was shown that the amount of carbohydrates accumulated depends on the growth rate of the cells and is mainly determined by the duration of the G1 phase. Both trehalose and glycogen increase viability by functioning as reserve carbohydrates under nutrient deprivation. On the other hand, accumulation of these carbohydrates increases the G1 phase duration under low nutrient supply and increases the reproduction rate. The integration of phosphorylation of Slt2 and reserve carbohydrate accumulation in the molecular mechanism of cell cycle progression of S. cerevisiae is discussed.