Interaction between ATM protein and c-Abl in response to DNA damage

Nature. 1997 May 29;387(6632):520-3. doi: 10.1038/387520a0.

Abstract

The gene mutated in the autosomal recessive disorder ataxia telangiectasia (AT), designated ATM (for 'AT mutated'), is a member of a family of phosphatidylinositol-3-kinase-like enzymes that are involved in cell-cycle control, meiotic recombination, telomere length monitoring and DNA-damage response. Previous results have demonstrated that AT cells are hypersensitive to ionizing radiation and are defective at the G1/S checkpoint after radiation damage. Because cells lacking the protein tyrosine kinase c-Abl are also defective in radiation-induced G1 arrest, we investigated the possibility that ATM might interact with c-Abl in response to radiation damage. Here we show that ATM binds c-Abl constitutively in control cells but not in AT cells. Our results demonstrate that the SH3 domain of c-Abl interacts with a DPAPNPPHFP motif (residues 1,373-1,382) of ATM. The results also reveal that radiation-induction of c-Abl tyrosine kinase activity is diminished in AT cells. These findings indicate that ATM is involved in the activation of c-Abl by DNA damage and this interaction may in part mediate radiation-induced G1 arrest.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ataxia Telangiectasia / metabolism*
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins
  • Cell Line
  • Cloning, Molecular
  • DNA Damage*
  • DNA-Binding Proteins
  • Enzyme Activation / radiation effects
  • Protein Binding / radiation effects
  • Protein-Serine-Threonine Kinases*
  • Proteins / genetics
  • Proteins / metabolism*
  • Proto-Oncogene Proteins c-abl / metabolism*
  • Radiation, Ionizing
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Tumor Suppressor Proteins
  • src Homology Domains

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Proteins
  • Recombinant Fusion Proteins
  • Tumor Suppressor Proteins
  • Proto-Oncogene Proteins c-abl
  • Ataxia Telangiectasia Mutated Proteins
  • Protein-Serine-Threonine Kinases