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Inactivation of B-type cyclin dependent kinases due to ubiquitin-mediated cyclin proteolysis is necessary for the exit from mitosis. In Saccharomyces cerevisiae, proteolysis is initiated at the onset of anaphase and remains active until Cln1 and Cln2 cyclins appear in late G1 of the subsequent cell cycle. A large particle called the anaphase-promoting complex (APC) which is composed of the TPR proteins Cdc16p/Cdc23p/Cdc27p and other proteins is required for B-type cyclin ubiquitination in both anaphase and during G1 phase. The APC has an essential role for the separation of sister chromatids and for the exit from mitosis, but until now it was unclear whether the persistence of APC activity throughout G1 had any physiological role. We show here that the APC is needed in G1 arrested cells to inhibit premature appearance of B-type cyclins and to prevent unscheduled initiation of DNA replication. When pheromone arrested cells of cdc16 and cdc23 mutants were shifted to the restrictive temperature, they underwent DNA replication in the presence of pheromone. DNA replication also occurred in a G1 arrest induced by G1 cyclin (Cln) depletion, indicating that mutant cells with a defective APC initiate DNA replication without the Cln G1 cyclins, which are normally needed for the onset of S-phase. Degradation of Clb2p, Clb3p and Clb5p depends on the APC. This suggests that accumulation of any one of the six B-type cyclin proteins could account for the precocious replication of cdc16 and cdc23 mutants.

Type

Journal article

Journal

J Cell Sci

Publication Date

07/1997

Volume

110 ( Pt 13)

Pages

1523 - 1531

Keywords

Anaphase, Anaphase-Promoting Complex-Cyclosome, Animals, Apc6 Subunit, Anaphase-Promoting Complex-Cyclosome, Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome, Cell Cycle Proteins, Cyclin-Dependent Kinase Inhibitor Proteins, Cyclins, DNA Replication, DNA, Fungal, Eukaryotic Cells, Fungal Proteins, G1 Phase, Humans, Ligases, Mating Factor, Mutation, Peptides, Pheromones, S Phase, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Substrate Specificity, Ubiquitin-Protein Ligase Complexes, Ubiquitin-Protein Ligases