Phosphorylation of the Sic1 inhibitor of B-type cyclins in Saccharomyces cerevisiae is not essential but contributes to cell cycle robustness

Genetics. 2007 Jul;176(3):1541-55. doi: 10.1534/genetics.107.073494. Epub 2007 May 4.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Cycle*
  • Cyclin B / antagonists & inhibitors*
  • Cyclin G
  • Cyclin-Dependent Kinase Inhibitor Proteins
  • Cyclins / metabolism
  • Phosphorylation
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transcriptional Activation

Substances

  • Cyclin B
  • Cyclin G
  • Cyclin-Dependent Kinase Inhibitor Proteins
  • Cyclins
  • SIC1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins