• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM.

The ataxia telangiectasia mutant (ATM) protein kinase regulates the cell's response to DNA damage through the phosphorylation of proteins involved in cell-cycle checkpoints and DNA repair. However, the signal-transduction pathway linking DNA strand breaks to activation of ATM's kinase activity is not clearly defined. Here, we demonstrate that DNA damage induces the rapid acetylation of ATM. This acetylation depends on the Tip60 histone acetyltransferase (HAT). Suppression of Tip60 blocks the activation of ATM's kinase activity and prevents the ATM-dependent phosphorylation of p53 and chk2. Further, inactivation of Tip60 sensitizes cells to ionizing radiation. ATM forms a stable complex with Tip60 through the conserved FATC domain of ATM. The interaction between ATM and Tip60 is not regulated in response to DNA damage. Instead, the HAT activity of the ATM-Tip60 complex is specifically activated by DNA damage. Furthermore, this activation of Tip60 by DNA damage and the recruitment of the ATM-Tip60 complex to sites of DNA damage is independent of ATM's kinase activity. The results demonstrate that the Tip60 HAT plays a key role in the activation of ATM's kinase activity in response to DNA damage.

Pubmed ID: 16141325


  • Sun Y
  • Jiang X
  • Chen S
  • Fernandes N
  • Price BD


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

September 13, 2005

Associated Grants


Mesh Terms

  • Acetylation
  • Acetyltransferases
  • Ataxia Telangiectasia Mutated Proteins
  • Binding Sites
  • Cell Cycle Proteins
  • DNA Damage
  • DNA-Binding Proteins
  • Enzyme Activation
  • HeLa Cells
  • Histone Acetyltransferases
  • Humans
  • Mutation
  • Protein Binding
  • Protein Transport
  • Protein-Serine-Threonine Kinases
  • Signal Transduction
  • Tumor Suppressor Proteins