ATM: Proteins and Enzymes

Germline mutations in the Ataxia Telangiectasia-mutated (ATM) gene lead to the multi-symptom disorder A-T (Ataxia Telangiectasia). Immunodeficiency, neurodegeneration, premature aging, sensitivity to ionizing radiation, and a predisposition to certain types of cancer characterize A-T. The protein product of the gene mutated in A-T is a large protein kinase involved in cell cycle checkpoint and genotoxic stress responses. The ATM protein kinase exists as a dimer in the cell nucleus. Changes in DNA structure induced by genotoxic stress lead to activation of ATM and phosphorylation of S1981 in trans. Once S1981 is phosphorylated, the dimer dissociates and active ATM monomers signal to downstream targets.