Figure 1.

ATM and ATR DDR pathways. The ATM and ATR pathways respond to different types of DNA damage with separate sensors (purple), mediators (blue) and transducers (red). Synthetic lethality can be exploited for cells with aberrant DDR pathways. Cells harbouring LOF mutations in one pathway have increased reliance on the other pathway for DNA damage repair. Inhibition of the intact pathway prevents p53-mediated DNA repair, cell cycle arrest and apoptosis. This results in accumulation of unrepaired DNA damage, mitotic catastrophe triggering p53-independent cell death. Pharmacological agents targeting components of the ATM/ATR pathways currently in clinical development are highlighted.