Role of calcineurin and Mpk1 in regulating the onset of mitosis in budding yeast.

Signalling via calcium is probably involved in regulating eukaryotic cell proliferation, but details of its mechanism of action are unknown. In Schizosaccharomyces pombe, the onset of mitosis is determined by activation of a complex of the p34cdc2 protein kinase and a cyclin protein that is specific to the G2 phase of the cell cycle. This activation requires dephosphorylation of p34cdc2. Weel, a tyrosine kinase that inhibits p34cdc2 by phosphorylating it, is needed to determine the length of G2 phase. Here we show that calcium-activated pathways in Saccharomyces cerevisiae control the onset of mitosis by regulating Swel, a Weel homologue. Zds1 (also known as Oss1 and Hst1) is important in repressing the transcription of SWE1 in G2 phase. In the presence of high calcium levels, cells lacking Zds1 are delayed in entering mitosis. Calcineurin and Mpk1 regulate Swel activation at the transcriptional and posttranslational levels, respectively, and both are required for the calcium-induced delay in G2 phase. These cellular pathways also induce a G2-phase delay in response to hypotonic shock.