Cell cycle control: A system of interlinking oscillators

The cell cycle is the sequence of events through which a cell duplicates its genome, grows, and divides. Key cell cycle transitions are driven by oscillators comprising cyclin-dependent kinases and other kinases. Different cell cycle oscillators are inextricably linked to ensure orderly activation of oscillators. A recurring theme in their regulation is the abundance of auto-amplifying loops that ensure switch-like and unidirectional cell cycle transitions. The periodicity of many cell cycle oscillators is choreographed by inherent mechanisms that promote automatic inactivation, often involving dephosphorylation and ubiquitinmediated protein degradation. These inhibitory signals are subsequently suppressed to enable the next cell cycle to occur. Although the activation and inactivation of cell cycle oscillators are in essence autonomous during the unperturbed cell cycle, a number of checkpoint mechanisms are able to halt the cell cycle until defects are addressed. Together, these mechanisms orchestrate orderly progression of the cell cycle to produce more cells and to safeguard genome integrity.