Linkage of replication to start by the Cdk inhibitor Sic1.
In Saccharomyces cerevisiae, three G1 cyclins (Clns) are important for Start, the event committing cells to division. Sic1, an inhibitor of C1b-Cdc28 kinases, became phosphorylated at Start, and this phosphorylation depended on the activity of Clns. Sic1 was subsequently lost, which depended on the activity of Clns and the ubiquitin-conjugating enzyme Cdc34. Inactivation of Sic1 was the only nonredundant essential function of Clns, because a sic1 deletion rescued the inviability of the cln1 cln2 cln3 triple mutant. In sic1 mutants, DNA replication became uncoupled from budding. Thus, Sic1 may be a substrate of Cln-Cdc28 complexes, and phosphorylation and proteolysis of Sic1 may regulate commitment to replication at Start.
Schneider
B L
BL
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Yang
Q H
QH
Futcher
A B
AB
D064173:Anaphase-Promoting Complex-Cyclosome; D017489:CDC28 Protein Kinase, S cerevisiae / Q000037:antagonists & inhibitors / Q000378:metabolism; D002453:Cell Cycle; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016213:Cyclins / Q000378:metabolism; D004261:DNA Replication; D004271:DNA, Fungal / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism*; D008025:Ligases / Q000378:metabolism; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases
D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016213:Cyclins; D004271:DNA, Fungal; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; C086926:SIC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C577449:CDC34 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases; D017489:CDC28 Protein Kinase, S cerevisiae; D008025:Ligases