Cells undergo a complex cycle of growth and division that is referred to as the cell cycle. The cell cycle consists of four phases, G1 (GAP 1), S (synthesis), G2 (GAP 2) and M (mitosis). DNA replication occurs during S phase. When cells stop dividing temporarily or indefinitely, they enter a quiescent state called G0.
The cell cycle is tightly regulated by phosphorylation and dephosphorylation events, which are catalyzed by cyclin-dependent kinases (Cdks)/cyclin complex and phosphatases, respectively. There are three major regulatory checkpoints for cell cycle control. The first one is the G1 checkpoint. DNA damage before S phase inhibits Cdk2and stops cell cycle progression until the damage is repaired. If severe damage cannot be repaired, p53 is activated, thus inducing apoptosis. G2 checkpoint senses DNA damage after S phase by inhibiting Cdk1. Spindle checkpoint detects chromosome alignment by spindle and kinetochores. Defective spindle-kinetochore interaction arrests cells in metaphase and induces apoptosis. Checkpoints are the quality control device of the cell cycle. When checkpoint function is lost and cell growth become uncontrollable, cancers develop. Understanding the molecular mechanisms of cell cycle regulation is of great importance to cancer research.
Figure1 regulation of the cell cycle