Coordination of growth with cell division in the yeast Saccharomyces cerevisiae

Yeast cell growth and cell division are normally coordinated. The mechanism of this coordination can be examined by attempting to dissociate the two processes. We have arrested division (with the use of temperature-sensitive cell division cycle mutants) and observed the effect of this arrest on growth, and we have limited growth (by nutritional deprivation) and observed the effect of this limitation on division. Mutants blocked at various stages of the cell cycle were able to continue growth, as evidenced by increases in cell volume, mass, and protein content. Cells that had initiated cell cycles were able to complete their cycles and arrest in G1 even when growth was very severely restricted. Under these conditions the daughter cells produced were abnormally small. Such abnormally small cells did not initiate new cell cycles (i.e., did not bud or complete any of the three known gene-controlled steps (cdc28, cdc4, cdc7) in G1) after nutrients were restored until growth to a critical size had occurred. We have also prepared abnormally large cells (by arresting division temporarily with the appropriate mating pheromone); when such cells were allowed to bud, the buds produced were much smaller than the mother cells when cytokinesis occurred. We propose that the normal coordination of cell growth with cell division is a consequence of the following two relationships. (1) Growth, rather than progress through the DNA-division cycle, is normally rate-limiting for cell proliferation. (2) A specific early event in G1, at or before the event controlled by the cdc28 gene product, cannot be completed until a critical size is attained.