Fig. 1.

Overview of the DNA damage-induced checkpoint pathways. The ATM/CHK2 and ATR/CHK1 pathways are activated by DNA double-strand breaks or by DNA single-strand breaks and replication stress, respectively. Cell cycle checkpoints are induced primarily through p53, CHK2, CHK1 and p38/MK2, which are phosphorylated by ATM and ATR. Activated p53 leads to G1-phase arrest and induces apoptosis. The phosphorylation of CDC25 by CHK2 and CHK1 abolishes the activation of CDKs, thus stopping cell cycle progression either in S-phase or at the boundary of G2/M. Cancer cells deficient in p53 due to mutation or deletion lack the G1 checkpoint and are more dependent on the intra-S and G2/M checkpoints.