10.8: Negative Regulator Molecules
Several proteins negatively regulate the cell cycle to prevent replication from occurring before cells are ready. During G1, if a cell’s DNA is damaged, the protein p53 recruits enzymes to repair the DNA before the cell transitions to S phase. p53 also stimulates the production of the Cdk inhibitor, p21, which binds to Cdk/cyclin complexes, inhibiting their activity and arresting the cell cycle. If the DNA damage is too much to overcome, p53 can prompt apoptosis, cell death, to prevent duplication of damaged DNA.
Another protein, Retinoblastoma protein, or Rb, can slow the cell cycle by binding to transcription factors, such as E2F, to block the transcription of genes necessary for the G1 to S transition. Once the cell grows to a sufficient size for division, Rb is phosphorylated and becomes inactive, releases E2F, and these genes can now be transcribed and translated into enzymes required for S phase.