Cdc6 cooperates with Sic1 and Hct1 to inactivate mitotic cyclin-dependent kinases.
Exit from mitosis requires the inactivation of mitotic cyclin-dependent kinases (CDKs). In the budding yeast, Saccharomyces cerevisiae, inactivation of CDKs during late mitosis involves degradation of B-type cyclins as well as direct inhibition of cyclin-CDK complexes by the CDK-inhibitor protein Sic1 (refs 1,2,3). Several striking similarities exist between Sic1 and Cdc6, a DNA replication factor essential for the formation of pre-replicative complexes at origins of DNA replication. Transcription of both genes is activated during late mitosis by a process dependent on Swi5 (ref. 10). Like Sic1, Cdc6 binds CDK complexes in vivo and downregulates them in vitro. Here we show that Cdc6, like Sic1, also contributes to inactivation of CDKs during late mitosis in S. cerevisiae. Deletion of the CDK-interacting domain of Cdc6 does not inhibit the function of origins of DNA replication during S phase, but instead causes a delay in mitotic exit; this delay is accentuated in the absence of Sic1 or of cyclin degradation. By contributing to mitotic exit and inactivation of CDKs, Cdc6 helps to create the conditions that are required for its subsequent role in the formation of pre-replicative complexes at origins of DNA replication.
Calzada
A
A
Instituto de Microbiología-Bioquímica, Departemento de Microbiología y Genética, Universidad de Salamanca, CSIC, Spain.
Sacristán
M
M
Sánchez
E
E
Bueno
A
A
D064200:Cdh1 Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D019926:Cyclin B / Q000378:metabolism; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004261:DNA Replication; D004271:DNA, Fungal / Q000096:biosynthesis / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D008938:Mitosis; D016296:Mutagenesis; D018741:Replication Origin; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins
C066503:CDC6 protein, S cerevisiae; C577583:CDH1 protein, S cerevisiae; C093749:CLB2 protein, S cerevisiae; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins; D019926:Cyclin B; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D004271:DNA, Fungal; D005656:Fungal Proteins; C086926:SIC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D018844:Cyclin-Dependent Kinases