Fig. 2.

The DNA damage-induced checkpoint mechanisms are depicted in this schematic representation. DNA double-strand breakage or DNA single-strand breaks and replication stress stimulate the ATM/CHK2 and ATR/CHK1 mechanisms, accordingly. Cell cycle checkpoints are predominantly activated by ATM and ATR phosphorylation of p53, CHK2, CHK1, and p38/MK2. Activated p53 causes G1-phase inhibition and apoptosis in cells.The phosphorylation of CDC25 by CHK2 and CHK1 prevents CDK expression, halting cellular proliferation in S-phase or at the G2/M transition. Cancerous cells lacking the G1 checkpoint due to mutation or loss of p53 seem to be more reliant on the intra-S and G2/M checkpoints.