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Additional Cell Cycle Checkpoints

There are 1X1012 cell divisions taking place in the human body on a daily basis.
The cell cycle has designated checkpoints to ensure accurate "carbon copies" of the mother cell DNA. In addition to Rb, there are two more checkpoints during the G1 to S transition.
If DNA damage is discovered during the G1 phase, the cell cycle must be halted to prevent inaccurate DNA from being replicated during the S phase. To halt cell cycle progression, two mechanisms can be carried out by two tumor suppressor proteins (Figure 2 below):
  • TGFβ (transforming growth factor beta) can activate a cell cycle inhibitor called p27. Activated p27 blocks activity of the cyclin D-CDK4 complex, making this protein complex unable to inactivate Rb, the G1 brake. The cell cycle therefore remains at the G1 phase without progressing to the S phase.
  • p53 can activate a cell cycle inhibitor called p21. Activated p21 blocks activity of the cyclin D-CDK4 complex. This results in the cell cycle being stuck in the G1 phase.
Both of these mechanisms serve the cell by preserving the fidelity of genetic materials and preventing faulty DNA from being replicated.