The Telomeric Protein TRF2 Binds the ATM Kinase and Can Inhibit the ATM-Dependent DNA Damage Response
AUTOR(ES)
Karlseder, Jan
FONTE
Public Library of Science
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=509302Documentos Relacionados
- Phosphorylation of Hdmx mediates its Hdm2- and ATM-dependent degradation in response to DNA damage
- Rapid ATM-dependent phosphorylation of MDM2 precedes p53 accumulation in response to DNA damage
- Selective induction of E2F1 in response to DNA damage, mediated by ATM-dependent phosphorylation
- Involvement of the cohesin protein, Smc1, in Atm-dependent and independent responses to DNA damage
- Oxidative damage in telomeric DNA disrupts recognition by TRF1 and TRF2