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. 2014 Jun 3;57(19):7859–7873. doi: 10.1021/jm500415t

Figure 4.

Figure 4

Checkpoint pathways and cell cycle regulations. DNA damage caused by physical, chemical, and biological factors, such as oncogene activation, activates phosphatidylinositol 3-kinase related kinases ATM and ATR, leading to the activation of CHK2, CHK1, and p38/MK2, which further regulate activity and stability of cell cycle regulators, including p53 and CDC25. p53/p21 is the major regulator of G1/S checkpoint. The loss of p53 function in cancer cells makes the cells addicting to the S and/or G2/M checkpoints for DNA repaire and survival. Inhibiting S and/or G2/M checkpoint regulators may induce synthetic lethality in p53 mutant cells when DNA is damaged. Arrow indicates activation, and the line terminating with a black circle indicates suppression.