Cell Cycle Regulation

The cell cycle consists of three states: quiescent, interphase, and mitosis, further divided into phases G0, G1, S, G2, and M. The quiescent state (G0) includes cells like neurons and cardiac muscle. Interphase comprises G1, S, and G2, while mitosis includes prophase, metaphase, anaphase, and telophase.

Major cell cycle checkpoints occur at the end of G1, the end of G2, and during metaphase of the M phase. Progression through these checkpoints is regulated by cyclins, cyclin-dependent kinases (CDKs), and tumor suppressors.

During the G1 phase, cell cycle progression is controlled by tumor suppressor genes, transcription factors, DNA damage detectors, and signaling molecules. E2F regulates transcription genes and cyclin-dependent kinases.

If there is significant DNA damage, p53 stimulates the production of p21, which inhibits cyclin-CDK complexes, arresting the cell cycle until the damage is repaired. The retinoblastoma protein inhibits E2F expression, but cyclin D-CDK4 and cyclin D-CDK6 complexes phosphorylate Rb, inactivating it and allowing E2F expression.

Cyclin A-CDK2 is required for DNA synthesis in the S phase. Cyclin A-CDK1 and cyclin B-CDK1 promote the events of mitosis. The anaphase-promoting complex causes ubiquitination and destruction of cyclin A-CDK1 and cyclin B-CDK1, leading to the termination of the M phase.

The G2 phase and mitosis are the most radiosensitive phases, while the latter part of the S phase is the least radiosensitive.