Regulation of cell cycle progression by Swe1p and Hog1a following hypertonic stress

Exposure of yeast cells to an increase in external osmolarity induces a tem porary growth arrest. Recovery from this stress is mediated by the accumula tion of intracellular glycerol and the transcription of several stress resp onse genes. Increased external osmolarity causes a transient accumulation o f 1N and 2N cells and a concomitant depletion of S phase cells. Hypertonic stress triggers a cell cycle delay in G2 phase cells that appears distinct from the morphogenesis checkpoint, which operates in early S phase cells. H ypertonic stress causes a decrease in CLB2 mRNA, phosphorylation of Cdc28p, and inhibition of Clb2p-Cdc28p kinase activity, whereas Clb2 protein level s are unaffected. Like the morphogenesis checkpoint, the osmotic stress-ind uced G2 delay is dependent upon the kinase Swe1p, but is not tightly correl ated with inhibition of Clb2p-Cdc28p kinase activity. Thus, deletion of SWE 1 does not prevent the hypertonic stress-induced inhibition of Clb2p-Cdc28p kinase activity. Mutation of the Swe1p phosphorylation site on Cdc28p (Y19 ) does not fully eliminate the Swe1p-dependent cell cycle delay, suggesting that Swe1p may have functions independent of Cdc28p phosphorylation. Conve rsely, deletion of the mitogen-activated protein kinase HOG1 does prevent C lb2p-Cdc28p inhibition by hypertonic stress, but does not block Cdc28p phos phorylation or alleviate the cell cycle delay. However, Hog1p does contribu te to proper nuclear segregation after hypertonic stress in tells that lack Swe1p. These results suggest a hypertonic stress-induced cell cycle delay in G2 phase that is mediated in a novel way by Swe1p in cooperation with Ho g1p.