ATM (DNA-damage-response gene)

ATM (ataxia-telangiectasia mutated) encodes a serine/threonine protein kinase that is the master activator of the DNA damage response to double-strand breaks; upon activation it phosphorylates hundreds of substrates including H2AX, CHK2, p53, and BRCA1 to coordinate cell-cycle arrest, DNA repair, and apoptosis. Biallelic loss-of-function mutations cause ataxia-telangiectasia, a recessive syndrome characterized by cerebellar neurodegeneration, immunodeficiency, radiation sensitivity, and a cancer risk exceeding 30%. Heterozygous ATM carriers (~1% of the population) have intermediate cancer risk — particularly for breast and colorectal cancer — and recent data suggest moderately elevated cardiovascular disease risk, placing ATM among the clinically actionable cancer-predisposition genes. In longevity biology, compromised ATM function exemplifies how defects in the DNA damage response accelerate hallmarks of aging including genomic instability and inflammation.