TI  - Interaction between  <prot>ATM</prot>  protein and  <prot>c-Abl</prot>  in response to DNA damage.
PG  - 520-3
AB  - The gene mutated in the autosomal recessive disorder ataxia telangiectasia
      (AT), designated <prot>ATM</prot> (for '<prot>AT mutated</prot>'), 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 <prot>c-Abl</prot> are also defective in radiation-induced G1 arrest,
      we investigated the possibility that <prot>ATM</prot> might interact with <prot>c-Abl</prot> in
      response to radiation damage. Here we show that  <prot>ATM</prot>  binds  <prot>c-Abl</prot> 
      constitutively in control cells but not in AT cells. Our results
      demonstrate that the SH3 domain of  <prot>c-Abl</prot>  interacts with a DPAPNPPHFP motif
      (residues 1,373-1,382) of  <prot>ATM</prot> . The results also reveal that
      radiation-induction of <prot>c-Abl</prot> tyrosine kinase activity is diminished in AT
      cells. These findings indicate that  <prot>ATM</prot>  is involved in the activation of
       <prot>c-Abl</prot>  by DNA damage and this interaction may in part mediate
      radiation-induced G1 arrest.
AD  - Joint Center for Radiation Therapy, Dana Farber Cancer Institutes, Boston,
