Figure 6.

Multiple oscillatory circuits are present in the skeleton, 5-variable model for the Cdk network. All these circuits are based on a negative feedback loop and can generate sustained oscillations of the cyclin/Cdk complexes involved in the circuit. Oscillators A (a) and B (b) involve the transcription factor E2F, cyclin D/Cdk4–6, cyclin E/Cdk2 and cyclin A/Cdk2, but not the cyclin B/Cdk1 complex and the protein Cdc20. Thus, they can produce sustained oscillations of Cdk2, which is responsible for DNA replication, without oscillation of Cdk1, which is responsible for the G2/M transition. In these conditions, cells go through multiple rounds of DNA replication without passing through mitosis. This phenomenon corresponds to endoreplication. Oscillator C (c) involves cyclin A/Cdk2 and cyclin B/Cdk1, and can therefore be viewed as a mitotic oscillator.