The Saccharomyces cerevisiae protein kinase Dbf2 carries out an essential function in late mitosis, and its kinase activity is cell-cycle regulated around anaphase/telophase. We have isolated SDB25, a high copy suppressor of temperature-sensitive dbf2 mutants, and genetic analysis suggests that the two proteins may function in parallel pathways in late mitosis. SDB25 encodes p40, a previously characterized substrate and potent inhibitor of Cdc28 kinase activity. Sdb25 is a phosphoprotein, and Sdb25 immunoprecipitates have a histone H1 kinase activity that is CDC28-dependent. Remarkably, Sdb25 transcript levels, protein levels, and associated kinase activity are precisely cell-cycle regulated, sharing a common peak in late mitosis. Moreover, Sdb25 protein levels and associated kinase activity are sharply up-regulated at the peak of Dbf2 kinase activity in cells released from a dbf2 ts block. The Sdb25 protein then disappears around Start in the next cell cycle. This indicates that SDB25 function is confined to M/GI, and morphological analysis of sdb25A cells supports this conclusion. Our data suggest that Sdb25 functions in a pathway in late mitosis leading to the down-regulation of Cdc28 kinase activity as cells traverse the M/G1 boundary.

Deactivation of the B cyclin kinase (Cdc28/Clb) drives the telophase to G1 cell cycle transition. Here we investigate one of the control pathways that contributes to kinase deactivation, involving the cell cycle-regulated production of the cdk inhibitor Sic1. We show that the cell cycle timing of SIC1 expression depends on the transcription factor Swi5, and that Swi5-dependent SIC1 expression begins during telophase. In contrast to Swi5, the related transcription factor Ace2, which can also induce SIC1 expression, is not active during telophase. The functional consequence of Swi5-regulated SIC1 expression in vivo is that both sic1Δ and swi5Δ strains have identical mitotic exit-related phenotypes. First, both are synthetically lethal with dbf2Δ, resulting in cell cycle arrest in telophase. Second, both are hypersensitive to overexpression of the B cyclin CLB2. Thus, Swi5-dependent activation of the SIC1 gene contributes to the deactivation of the B cyclin kinase, and hence exit from mitosis.

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