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 weight protein predominantly confined to the nucleus of human fibroblasts, but is present in both nuclear and microsomal fractions from human lymphoblast cells and peripheral blood lymphocytes. ATM protein levels and localization remain constant throughout all stages of the cell cycle. 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-irradiation and the radiomimetic drug neocarzinostatin had no effect on ATM protein 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 regulation following genome damage.
Brown
K D
KD
Laboratory of Gene Transfer, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Ziv
Y
Y
Sadanandan
S N
SN
Chessa
L
L
Collins
F S
FS
Shiloh
Y
Y
Tagle
D A
DA
D000906:Antibodies / Q000276:immunology; D064007:Ataxia Telangiectasia Mutated Proteins; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D018797:Cell Cycle Proteins; D002460:Cell Line; D004249:DNA Damage / Q000235:genetics*; D004268:DNA-Binding Proteins; D005455:Fluorescent Antibody Technique; D005720:Gamma Rays; D006801:Humans; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000378:metabolism*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000032:analysis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000302:isolation & purification; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation; D009353:Zinostatin / Q000494:pharmacology
D000906:Antibodies; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D011506:Proteins; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D009353:Zinostatin; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases