Cell cycle: G1/S phase transition

Cell cycle progression is a tightly regulated process that depends on the expression and activation of positive and negative regulators of the cell cycle machinery. The primary G1/S cell cycle checkpoint controls the commitment through the G1 phase to enter into the DNA synthesis S phase. Before the passage of the restriction point, activation of CCND- and CCNE-dependent CDKs initiates a sequence of events that eventually leads to the initiation of a full cell cycle. Under favorable growth conditions, CDK4/6 associate with CCNDs, phosphorylate and inactivate pRB, allowing the release of E2F and the transcription of its target genes. Under stress conditions (e,g DNA damage), the activity of CDKs can be blocked by natural inhibitors, CKI, belonging either to the INK4 or the CIP families, resulting in cell cycle arrest.