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Molecular and Cellular Biology, July 2009, p. 3597-3604, Vol. 29, No. 13
0270-7306/09/$08.00+0 doi:10.1128/MCB.00944-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Department of Medical and Molecular Genetics,1 Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana 462022
Received 13 June 2008/ Returned for modification 18 August 2008/ Accepted 14 April 2009
Protein kinases of the phosphatidylinositol 3-kinase-like kinase family, originally known to act in maintaining genomic integrity via DNA repair pathways, have been shown to also function in telomere maintenance. Here we focus on the functional role of DNA damage-induced phosphorylation of the essential mammalian telomeric DNA binding protein TRF2, which coordinates the assembly of the proteinaceous cap to disguise the chromosome end from being recognized as a double-stand break (DSB). Previous results suggested a link between the transient induction of human TRF2 phosphorylation at threonine 188 (T188) by the ataxia telangiectasia mutated protein kinase (ATM) and the DNA damage response. Here, we report evidence that X-ray-induced phosphorylation of TRF2 at T188 plays a role in the fast pathway of DNA DSB repair. These results connect the highly transient induction of human TRF2 phosphorylation to the DNA damage response machinery. Thus, we find that a protein known to function in telomere maintenance, TRF2, also plays a functional role in DNA DSB repair.
Published ahead of print on 27 April 2009.
# These authors contributed equally to this work.
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