Original Article

Cdc28 Activates Exit from Mitosis in Budding Yeast

Correspondence to: Andrew W. Murray, University of California, San Francisco, Department of Physiology, Box 0444, 513 Parnassus Avenue, San Francisco, CA 94143-0444. Tel:(415) 476-0364 Fax:(415) 476-4929 E-mail:amurray{at}cgl.ucsf.edu.

The activity of the cyclin-dependent kinase 1 (Cdk1), Cdc28, inhibits the transition from anaphase to G1 in budding yeast. CDC28-T18V, Y19F (CDC28-VF), a mutant that lacks inhibitory phosphorylation sites, delays the exit from mitosis and is hypersensitive to perturbations that arrest cells in mitosis. Surprisingly, this behavior is not due to a lack of inhibitory phosphorylation or increased kinase activity, but reflects reduced activity of the anaphase-promoting complex (APC), a defect shared with other mutants that lower Cdc28/Clb activity in mitosis. CDC28-VF has reduced Cdc20- dependent APC activity in mitosis, but normal Hct1- dependent APC activity in the G1 phase of the cell cycle. The defect in Cdc20-dependent APC activity in CDC28-VF correlates with reduced association of Cdc20 with the APC. The defects of CDC28-VF suggest that Cdc28 activity is required to induce the metaphase to anaphase transition and initiate the transition from anaphase to G1 in budding yeast.

Key Words: anaphase-promoting complex, Hct1, Cdc20, Pds1, sister chromatid separation

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