The Molecular Mechanism of Cell Cycle Control

The fission yeast has been genetically engineered to simplify the cell cycle control system so it can run using only a single CDK. This has led to the proposal that the core principle underlying the control is rising general CDK activity as the cell increases in mass. This has been confirmed by mass spec analyses and in vivo protein kinase assays. In addition to cell cycle order being established through quantitative increase in CDK activity, localisation of that activity is also important. The centrosome has long been suggested as a global cell cycle organiser, and CDK is localised there. This localisation is brought about by a hydrophobic patch in the cyclin component of the CDK, and without that patch centrosome localisation is lost and cells cannot undergo M-phase. In vivo CDK assays have shown that this patch is necessary for the phosphorylation of a set of centrosomally located substrates which can only be phosphorylated by high CDK activity. Therefore, both temporally determined increases responding to cell mass increase and spatial ordering of CDK activity are central to the mechanism underpinning the developmental sequence of cell cycle events.