Phosphorylation control - The key process among the chemical events that trigger the successive stages of the cell cycle is the phosphorylation of a number of nuclear proteins (including histone H1). The key enzymes are a set of kinases.

Yeast control - cdc2 (from yeast) is a serine/threonine kinase whose activation requires association with specific small proteins called cyclins. In yeast, one cyclin activates cdc2 at the start of S phase, another reactivates it at the beginning of mitosis.

Cyclins/cyclin-dependent kinases in higher eukaryotes - In higher eukaryotes, there are several "cyclin-dependent kinases" and a number of cyclins to associate with them. Each transition in the cell cycle appears to have a unique cyclin/kinase complex as its trigger. A simplified view of the roles of these proteins in mammalian cells is shown in Figure 28.16. The cyclin-dependent kinase CDK2 is involved in the entrance to S-phase, and cdc2, with cyclins A and B, regulates mitosis.

Control of the cell cycle triggers - The cell cycle triggers themselves are under strict control. Synthesis of cyclins is determined, at least in part, by growth hormones. cdc2 is phosphorylated at entry to the G2 phase, but must be dephosphorylated for mitosis to continue. If DNA is damaged or replication forks are stalled, dephosphorylation of cdc2 is prevented and this stops mitosis. This is a so-called checkpoint for the cell cycle.

Second checkpoint - Another checkpoint occurs when the protein p53 detects DNA damage. When damage is detected, p53 activates transcription of the gene PicI, the product of which binds to CDCKs, blocking the cell in the G1 phase and frequently leading to apoptosis. If p53 is unable to function, potentially cancerous cells with damaged DNA will be able to replicate.