FIGURE 3.

ATM controls cellular survival in response to DNA damage through multiple pathways. DNA damage activates apoptosis in a p53-dependent manner in some cell types such as lymphocytes. p53 is activated by parallel pathways controlled by the Mre11 complex and ATM (black arrows) or DNA-PK and Chk2 (red arrows). The Mre11 complex is required for ATM activation and plays downstream roles mediating access to targets such as BID. Chk2 can act independently of ATM and may be a target of DNA-PK that is required for ATM-independent p53-dependent apoptosis. MDM2 phosphorylation by ATM is required for p53 stability and activity. ATM is also required for the Chk1 sensitized cell death pathway. ATM phosphorylates p53-induced protein with a death domain (PIDD) when Chk1 is inhibited favoring RIP associated Ich-1/CED homologous protein with death domain (RAIDD) binding that promotes caspase 2 activation and cell death. Murine alleles or small molecules (Chk1 or DNA-PKcs inhibitors) that affect these pathways are noted in italics. ATM targets are indicated with a red P.