Phosphorylation of the Sic1 inhibitor of B-type cyclins in Saccharomyces cerevisiae is not essential but contributes to cell cycle robustness.
In budding yeast, B-type cyclin (Clb)-dependent kinase activity is essential for S phase and mitosis. In newborn G(1) cells, Clb kinase accumulation is blocked, in part because of the Sic1 stoichiometric inhibitor. Previous results strongly suggested that G(1) cyclin-dependent Sic1 phosphorylation, and its consequent degradation, is essential for S phase. However, cells containing a precise endogenous gene replacement of SIC1 with SIC1-0P (all nine phosphorylation sites mutated) were fully viable. Unphosphorylatable Sic1 was abundant and nuclear throughout the cell cycle and effectively inhibited Clb kinase in vitro. SIC1-0P cells had a lengthened G(1) and increased G(1) cyclin transcriptional activation and variable delays in the budded part of the cell cycle. SIC1-0P was lethal when combined with deletion of CLB2, CLB3, or CLB5, the major B-type cyclins. Sic1 phosphorylation provides a sharp link between G(1) cyclin activation and Clb kinase activation, but failure of Sic1 phosphorylation and proteolysis imposes a variable cell cycle delay and extreme sensitivity to B-type cyclin dosage, rather than a lethal cell cycle block.
Cross
Frederick R
FR
The Rockefeller University, New York, New York 10021, USA. fcross@rockefeller.edu
Schroeder
Lea
L
Bean
James M
JM
D002453:Cell Cycle; D019926:Cyclin B / Q000037:antagonists & inhibitors*; D056746:Cyclin G; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016213:Cyclins / Q000378:metabolism; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015533:Transcriptional Activation
D019926:Cyclin B; D056746:Cyclin G; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016213:Cyclins; C086926:SIC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins