@article {Cross1541, author = {Cross, Frederick R. and Schroeder, Lea and Bean, James M.}, title = {Phosphorylation of the Sic1 Inhibitor of B-Type Cyclins in Saccharomyces cerevisiae Is Not Essential but Contributes to Cell Cycle Robustness}, volume = {176}, number = {3}, pages = {1541--1555}, year = {2007}, doi = {10.1534/genetics.107.073494}, publisher = {Genetics}, abstract = {In budding yeast, B-type cyclin (Clb)-dependent kinase activity is essential for S phase and mitosis. In newborn G1 cells, Clb kinase accumulation is blocked, in part because of the Sic1 stoichiometric inhibitor. Previous results strongly suggested that G1 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 G1 and increased G1 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 G1 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.}, issn = {0016-6731}, URL = {https://www.genetics.org/content/176/3/1541}, eprint = {https://www.genetics.org/content/176/3/1541.full.pdf}, journal = {Genetics} }