Résumé
When yeast cells reach a critical size, they initiate bud formation, spindle pole body duplication, and DNA replication almost simultaneously. All three events depend on activation of Cdc28 protein kinase by the G1 cyclins Cln1, −2, and −3. We show that DNA replication also requires activation of Cdc28 by B-type (Clb) cyclins. A sextuple
clb1–6 mutant arrests as multibudded G1 cells that resemble cells lacking the Cdc34 ubiquitin-conjugating enzyme.
cdc34 mutants cannot enter S phase because they fail to destroy p40
SIC1
, which is a potent inhibitor of Clb but not Cln forms of the Cdc28 kinase. In wild-type cells, p40
SIC1
protein appears at the end of mitosis and disappears shortly before S phase. Proteolysis of a cyclin-specific inhibitor of Cdc28 is therefore an essential aspect of the G1 to S phase transition.