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

• Yingli Sun

  Department of Radiation Oncology, Dana–Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115

• Xiaofeng Jiang

  Department of Radiation Oncology, Dana–Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115

• Shujuan Chen

  Department of Radiation Oncology, Dana–Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115

• Norvin Fernandes

  Department of Radiation Oncology, Dana–Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115

• Brendan D. Price

  Department of Radiation Oncology, Dana–Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115

抄録

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.

収録刊行物

• Proceedings of the National Academy of Sciences

  Proceedings of the National Academy of Sciences 102 (37), 13182-13187, 2005-09-02

  Proceedings of the National Academy of Sciences

キーワード

• Multidisciplinary

詳細情報

• CRID: 1364233270201318272
• NII論文ID: 80017502626
• DOI: 10.1073/pnas.0504211102
• ISSN: 10916490
• ISSN: 00278424
• Web Site: https://pnas.org/doi/pdf/10.1073/pnas.0504211102
• データソース種別:
  • Crossref
  • CiNii Articles