ATM
ATM is the apical kinase of the DNA double-strand-break response and a founding member of the PIKK family. It is maintained as an inactive dimer and is activated at DSBs through recruitment by the MRN complex; once engaged it phosphorylates a broad network of Ser/Thr-Gln targets, including Chk2, p53, H2AX, BRCA1 and KAP1, triggering checkpoint arrest, DNA repair or apoptosis. Germline ATM loss causes ataxia-telangiectasia, and heterozygous carriers face elevated breast-cancer risk. Clinically, ATM inhibitors are being developed as radiosensitizers and chemo-potentiators. Recombinant ATM supports kinase assays, DNA damage response reconstitution and inhibitor discovery.
