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The telomeric protein TRF2 binds the ATM kinase and can inhibit the ATM-dependent DNA damage response.

Publication ,  Journal Article
Karlseder, J; Hoke, K; Mirzoeva, OK; Bakkenist, C; Kastan, MB; Petrini, JHJ; de Lange, T
Published in: PLoS Biol
August 2004

The telomeric protein TRF2 is required to prevent mammalian telomeres from activating DNA damage checkpoints. Here we show that overexpression of TRF2 affects the response of the ATM kinase to DNA damage. Overexpression of TRF2 abrogated the cell cycle arrest after ionizing radiation and diminished several other readouts of the DNA damage response, including phosphorylation of Nbs1, induction of p53, and upregulation of p53 targets. TRF2 inhibited autophosphorylation of ATM on S1981, an early step in the activation of this kinase. A region of ATM containing S1981 was found to directly interact with TRF2 in vitro, and ATM immunoprecipitates contained TRF2. We propose that TRF2 has the ability to inhibit ATM activation at telomeres. Because TRF2 is abundant at chromosome ends but not elsewhere in the nucleus, this mechanism of checkpoint control could specifically block a DNA damage response at telomeres without affecting the surveillance of chromosome internal damage.

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Published In

PLoS Biol

DOI

EISSN

1545-7885

Publication Date

August 2004

Volume

2

Issue

8

Start / End Page

E240

Location

United States

Related Subject Headings

  • Up-Regulation
  • Tumor Suppressor Proteins
  • Tumor Suppressor Protein p53
  • Transfection
  • Telomeric Repeat Binding Protein 2
  • Telomere
  • TATA Box Binding Protein-Like Proteins
  • Radiation, Ionizing
  • Protein Serine-Threonine Kinases
  • Protein Binding
 

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Karlseder, J., Hoke, K., Mirzoeva, O. K., Bakkenist, C., Kastan, M. B., Petrini, J. H. J., & de Lange, T. (2004). The telomeric protein TRF2 binds the ATM kinase and can inhibit the ATM-dependent DNA damage response. PLoS Biol, 2(8), E240. https://doi.org/10.1371/journal.pbio.0020240
Karlseder, Jan, Kristina Hoke, Olga K. Mirzoeva, Christopher Bakkenist, Michael B. Kastan, John H. J. Petrini, and Titia de Lange. “The telomeric protein TRF2 binds the ATM kinase and can inhibit the ATM-dependent DNA damage response.PLoS Biol 2, no. 8 (August 2004): E240. https://doi.org/10.1371/journal.pbio.0020240.
Karlseder J, Hoke K, Mirzoeva OK, Bakkenist C, Kastan MB, Petrini JHJ, et al. The telomeric protein TRF2 binds the ATM kinase and can inhibit the ATM-dependent DNA damage response. PLoS Biol. 2004 Aug;2(8):E240.
Karlseder, Jan, et al. “The telomeric protein TRF2 binds the ATM kinase and can inhibit the ATM-dependent DNA damage response.PLoS Biol, vol. 2, no. 8, Aug. 2004, p. E240. Pubmed, doi:10.1371/journal.pbio.0020240.
Karlseder J, Hoke K, Mirzoeva OK, Bakkenist C, Kastan MB, Petrini JHJ, de Lange T. The telomeric protein TRF2 binds the ATM kinase and can inhibit the ATM-dependent DNA damage response. PLoS Biol. 2004 Aug;2(8):E240.
Journal cover image

Published In

PLoS Biol

DOI

EISSN

1545-7885

Publication Date

August 2004

Volume

2

Issue

8

Start / End Page

E240

Location

United States

Related Subject Headings

  • Up-Regulation
  • Tumor Suppressor Proteins
  • Tumor Suppressor Protein p53
  • Transfection
  • Telomeric Repeat Binding Protein 2
  • Telomere
  • TATA Box Binding Protein-Like Proteins
  • Radiation, Ionizing
  • Protein Serine-Threonine Kinases
  • Protein Binding