Skip to main content
. Author manuscript; available in PMC: 2019 Dec 11.
Published in final edited form as: Trends Mol Med. 2010 Nov 17;17(2):88–96. doi: 10.1016/j.molmed.2010.10.009

Figure 1. Cell cycle checkpoints.

Figure 1.

The eukaryotic cell cycle consists of four phases called G1 (Gap 1), S (Synthesis), G2 (Gap 2) and M (Mitosis). Genotoxic and replicative stress activate checkpoints in order to delay cells from transitioning from one cell cycle phase to the next. p53 is required for cells to stop at the G1/S-border (G1 checkpoint) whereas CHK1 is required to prevent new replication origins from firing in S-phase (S-phase checkpoint) and to prevent cells from exiting G2- and entering into M-phase (G2 checkpoint). Although cells are able to activate the S- and G2- checkpoints in the absence of p53, they are unable to sustain these checkpoints for as long as normal cells (A, B). Most cancer cells lack a functional p53 pathway and therefore are unable to arrest in G1 when their DNA is damaged, but they are able to activate the S- and G2-checkpoints through the CHK1 pathway. This gives the tumor cells time to repair any DNA damage and this promotes their survival (C). When p53 deficient cancer cells are subjected to genotoxic or replicative stress in combination with a CHK1 inhibitor they lose all three checkpoints, and progress through the cell cycle without repairing their DNA damage. This results in preferential killing of p53-deficient tumor cells (D).