期刊
PLOS BIOLOGY
卷 2, 期 8, 页码 1150-1156出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pbio.0020240
关键词
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资金
- NCI NIH HHS [P30 CA021765, R01 CA071387, CA71387, CA21765] Funding Source: Medline
- NIA NIH HHS [R01 AG016642, AG016642] Funding Source: Medline
- NIGMS NIH HHS [R37 GM049046, GM07739, R37 GM059413, T32 GM007739, GM59413, GM49046, R01 GM049046, R01 GM059413, GM56888, R01 GM056888] Funding Source: Medline
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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