The Stability of the Cdc6 Protein Is Regulated by Cyclin-dependent Kinase/Cyclin B Complexes inSaccharomyces cerevisiae

• Published in: The Journal of biological chemistry Vol. 275; no. 13; pp. 9734 - 9741
• Main Authors: Calzada, Arturo, Sánchez, Mar, Sánchez, Elisa, Bueno, Avelino
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 31.03.2000; American Society for Biochemistry and Molecular Biology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.275.13.9734

The Saccharomyces cerevisiae Cdc6 protein is necessary for the formation of prereplicative complexes that are a prerequisite for firing origins during DNA replication in the S phase. In budding yeast, the presence of Cdc6 protein is normally restricted to the G1 phase of the cell cycle, at least partly because of its proteolytic degradation in the late G1/early S phase. Here we show that a Cdc28-dependent mechanism targets p57 CDC6 for degradation in mitotic-arrested budding yeast cells. Consistent with this observation, Cdc6–7 and Cdc6–8 proteins, mutants lacking Cdc28 phosphorylation sites, are stabilized relative to wild-type Cdc6. Our data also suggest a correlation between the absence of Cdc28/Clb kinase activity and Cdc6 protein stabilization, because a drop in Cdc28/Clb-associated kinase activity allows mitotic-arrested cells to accumulate Cdc6 protein. Finally, we also show that cdc28temperature-sensitive G1 mutants accumulate Cdc6 protein because of a post-transcriptional mechanism. Our data suggest that budding yeast cells target Cdc6 for degradation through a Cdc28-dependent mechanism in each cell cycle.