DOI: 10.1073/pnas.0504211102. A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM

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

10.1073/pnas.0504211102

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

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.

Bibliography

Sun, Y., Jiang, X., Chen, S., Fernandes, N., & Price, B. D. (2005). A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM. Proceedings of the National Academy of Sciences, 102(37), 13182â13187.

Authors 5

Yingli Sun (first)
Xiaofeng Jiang (additional)
Shujuan Chen (additional)
Norvin Fernandes (additional)
Brendan D. Price (additional)

References 34 Referenced 597

Dates

Type	When
Created	19 years, 11 months ago (Sept. 2, 2005, 8:34 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 12:38 p.m.)
Indexed	1 week, 5 days ago (Aug. 12, 2025, 5:54 p.m.)
Issued	19 years, 11 months ago (Sept. 2, 2005)
Published	19 years, 11 months ago (Sept. 2, 2005)
Published Online	19 years, 11 months ago (Sept. 2, 2005)
Published Print	19 years, 11 months ago (Sept. 13, 2005)

Funders 0

None

BibTeX

@article{Sun_2005, title={A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM}, volume={102}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0504211102}, DOI={10.1073/pnas.0504211102}, number={37}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Sun, Yingli and Jiang, Xiaofeng and Chen, Shujuan and Fernandes, Norvin and Price, Brendan D.}, year={2005}, month=sep, pages={13182–13187} }

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  "abstract": "<jats:p>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\u2013Tip60 complex is specifically activated by DNA damage. Furthermore, this activation of Tip60 by DNA damage and the recruitment of the ATM\u2013Tip60 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.</jats:p>",
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