Intriguingly, recent work demonstrated that DNA checkpoint control depends on the same transcription factors responsible for commitment point regulation 11. Subsequent studies showed that the broad mechanisms of eukaryotic G1 cell cycle control are highly conserved 7– 9, 10. RB is a potent inhibitor of G1–S transcription (that is, a transcriptional wave that initiates during G1 and is subsequently inactivated during S phase), and its discovery over 20 years ago first suggested the dependency of cell cycle commitment on transcriptional regulation in G1 (REFS 4 – 6). One notable regulatory protein that is often mutated in cancer is the tumour suppressor protein RB 3. The importance of DNA checkpoints and commitment point control for proper cell division is illustrated by the high frequency of mutations found in their constituent regulatory proteins during oncogenesis 2. This point is known as the ‘restriction point’ in animal cells and ‘start’ in yeast and is defined as the point after which a cell becomes committed to enter the cell cycle and progress through it independently of signals from the environment. Two crucial aspects of cell cycle regulation are the existence of DNA structure checkpoints, which arrest the cell cycle in response to DNA damage or incomplete replication, and the existence of a ‘commitment point’. The discovery of cyclins and cyclin-dependent kinases (CDKs), the elucidation of the mechanisms underlying transcriptional control and checkpoint signalling and the characterization of ubiquitin ligase regulatory pathways have revealed that general cell cycle regulatory principles are shared across eukaryotes. It proceeds through tightly regulated transitions to ensure that specific events take place in an orderly manner. The eukaryotic cell cycle is controlled by a regulatory network, the general features of which are conserved from yeast to humans 1.

Blueprint cdk2