- The cell‑cycle checkpoints are control systems that monitor the accuracy and timing of cell‑cycle events, ensuring that a cell only progresses when conditions are favourable and the genome is intact. These checkpoints act as surveillance mechanisms that pause the cycle if errors or damage are detected, allowing time for repair and preventing the propagation of mutations. They are essential for maintaining genomic stability, supporting normal development, and preventing diseases such as cancer.
- The G1 checkpoint, located at the G1/S transition, is the cell’s primary decision point. Here, the cell assesses whether it has sufficient nutrients, growth‑factor signalling, and energy reserves to commit to DNA replication. It also checks for DNA damage. If conditions are inadequate, the cell may enter a quiescent G0 state or delay progression until repairs are completed. Once the cell passes this checkpoint—often called the restriction point—it becomes committed to S‑phase entry and will continue through the cycle even if external signals are withdrawn.
- The G2 checkpoint operates before mitosis and ensures that DNA replication in S phase has been fully completed. It also verifies that no replication errors or DNA damage remain. If problems are detected, the cell halts progression and activates repair pathways. Only when the genome is fully replicated and structurally intact does the cell proceed into mitosis. This checkpoint prevents cells with incomplete or damaged DNA from entering division, thereby reducing the risk of chromosomal abnormalities.
- The spindle assembly checkpoint, active during metaphase of mitosis, monitors chromosome attachment to the mitotic spindle. Each chromosome must be correctly attached via its kinetochore and under proper tension before the cell is permitted to enter anaphase. Because chromosome separation is irreversible, this checkpoint is critical for preventing aneuploidy. If even a single kinetochore is unattached, the checkpoint delays progression until proper alignment is achieved.
- Together, these checkpoints form a multilayered defence system that ensures accurate DNA replication, faithful chromosome segregation, and controlled cell proliferation. Their failure—through mutations in checkpoint genes such as p53, ATM, ATR, or spindle‑checkpoint components—can lead to genomic instability and contribute to tumour development.
