THE ATAXIA-TELANGIECTASIA GENE-PRODUCT, A CONSTITUTIVELY EXPRESSED NUCLEAR-PROTEIN THAT IS NOT UP-REGULATED FOLLOWING GENOME DAMAGE

The product of the ataxia-telangiectasia gene (ATM) was identified by using an antiserum developed to a peptide corresponding to the deduced amino acid sequence, The ATM protein is a single, high-molecular weig ht protein predominantly confined to the nucleus of human fibroblasts, but is present in both nuclear and microsomal fractions from human ly mphoblast cells and peripheral blood lymphocytes, ATM protein levels a nd localization remain constant throughout all stages of the cell cycl e, Truncated ATM protein was not detected in lymphoblasts from ataxia- telangiectasia patients homozygous for mutations leading to premature protein termination, Exposure of normal human cells to gamma-irradiati on and the radiomimetic drug neocarzinostatin had no effect on ATR;I p rotein levels, in contrast to a noted rise in p53 levels over the same time interval, These findings are consistent with a role for the ATM protein in ensuring the fidelity of DNA repair and cell cycle regulati on following genome damage.