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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 p40SIC1, which is a potent inhibitor of Clb but not Cln forms of the Cdc28 kinase. In wild-type cells, p40SIC1 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.

Type

Journal article

Journal

Cell

Publication Date

21/10/1994

Volume

79

Pages

233 - 244

Keywords

Anaphase-Promoting Complex-Cyclosome, CDC28 Protein Kinase, S cerevisiae, Cell Cycle, Cyclin B, Cyclin-Dependent Kinase Inhibitor Proteins, Cyclins, Fungal Proteins, Ligases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligase Complexes, Ubiquitin-Protein Ligases