C: ell cycle checkpoints can enhance cell survival and liimit mutagenic events following DNA damage. Primary murine fibroblasts became deficient in a Gl clheckpoint activated by ionizing radiation (IF?) when b’oth wilcl-type~ 53 alleles were disrupted. In addition, c~ ells from patients with the radiosensitive, cancerprone disease ataxia-telangiectasia(AT) lacked the IR-induced increase in~ 53 protein levels seen in normal aells. Finally, IR induction of the human GADD45 gene, an induction that is also defective in AT cells, was deplendent on wild-type p53 function. Wild-type but not mlutant p53 bound strongly to a conserved element in the GADD45 gene, and a p53-containing nuclear factor, which bound this element, was detected in extracts from irradiated cells. Thus, we identified three participants (AT gene (s),~ 53, and GADD45) in a signal transduction pathway that controls cell cycle arrest following DNA damage; abnormalities in this pathway probably contribute to tumor development.