Activation of the G2/M checkpoint after DNA damage. In response to DNA damage, the ATM, ATR signaling pathway is activated, which leads to the phosphorylation and activation of Chk1 and Chk2 and to the subsequent phosphorylation of Cdc25. Phosphorylated Cdc25 is sequestered in the cytoplasm by 14-3-3 proteins, which prevents activation of cyclinB/Cdk1 by Cdc25 and results in G2 arrest. Activated ATM/ATR also activates p53-dependent signaling. This contributes to the maintenance of G2 arrest by upregulating 14-3-3, which sequesters Cdk1 in the cytoplasm. In addition, p53 induces the transactivation of p21, a Cdk inhibitor that binds to and inhibits cyclinB/Cdk1 complexes. P: phosphorylation.
Wang et al. Molecular Cancer 2009 8:8 doi:10.1186/1476-4598-8-8