Control of cell division in Saccharomyces cerevisiae by methionyl-tRNA.

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Abstract
It is suggested that 2 events are necessary for an asynchronous population of cells to undergo arrest in the G1 phase of the cell cycle upon nutrient starvation. First, passage through G1 must be prevented by a deficiency of some metabolic intermediate. Since this intermediate may act indirectly to arrest division, it is designated the "signal." Three conditions were found under which S. cerevisiae cells arrest division in G1: sulfate starvation of a prototroph, methionine starvation of an auxotroph, or a shift of a conditional methionyl-tRNA synthetase mutant [L-methionine:tRNAMet ligase (AMP-forming), EC6.1.1.10] to a restrictive condition. These results are interpreted to indicate that the signal for sulfate starvation in S. cerevisiae is generated near the end of the sulfate assimilation pathway (at or beyond the formation of methionyl-tRNA). As a unifying hypothesis, it is proposed that the signal for all nutrients is generated at the level of protein biosynthesis. A 2nd event necessary for G1 arrest is the provision of sufficient protein synthetic capacity for cells to finish the cycles that are in progress when the signal is generated. This necessity is demonstrated by the failure of the methionyl-tRNA synthetase mutant to undergo G1 arrest when protein synthesis is abruptly terminated by a shift to 36.degree. into methionine-deficient medium.