A. Calzada et al., The stability of the Cdc6 protein is regulated by cyclin-dependent kinase/cyclin B complexes in Saccharomyces cerevisiae, J BIOL CHEM, 275(13), 2000, pp. 9734-9741
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 pro
tein is normally restricted to the G(1) phase of the cell cycle, at least p
artly because of its proteolytic degradation in the late G(1)/early S phase
. Here we show that a Cdc28-dependent mechanism targets p57(CDC6) for degra
dation in mitotic arrested budding yeast cells. Consistent with this observ
ation, Cdc6-7 and Cdc6-8 proteins, mutants lacking Cdc28 phosphorylation si
tes, are stabilized relative to wild-type Cdc6, Our data also suggest a cor
relation between the absence of Cdc28/Clb kinase activity and Cdc6 protein
stabilization, because a drop in Cdc28/Clb-associated kinase activity allow
s mitotic-arrested cells to accumulate Cdc6 protein. Finally, we also show
that cdc28 temperature-sensitive G(1) mutants accumulate Cdc6 protein becau
se of a post-transcriptional mechanism. Our data suggest that budding yeast
cells target Cdc6 for degradation through a Cdc28-dependent mechanism in e
ach cell cycle.