{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T14:00:11Z","timestamp":1791208811680,"version":"4.1.0"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"43","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,10,25]]},"abstract":"<jats:p>Several protein kinases from diverse eukaryotes known to perform important roles in DNA repair have also been shown to play critical roles in telomere maintenance. Here, we report that the human telomere-associated protein TRF2 is rapidly phosphorylated in response to DNA damage. We find that the phosphorylated form of TRF2 is not bound to telomeric DNA, as is the ground form of TRF2, and is rapidly localized to damage sites. Our results suggest that the ataxia-telangiectasia-mutated (ATM) protein kinase signal-transduction pathway is primarily responsible for the DNA damage-induced phosphorylation of TRF2. Unlike DNA damage-induced phosphorylation of other ATM targets, the phosphorylated form of TRF2 is transient, being detected rapidly at DNA damage sites postirradiation, but largely dissipated by 2 hours. In addition, we report that the phosphorylated form of TRF2 is present at telomeres in cell types undergoing telomere-based crisis and a recombination-driven, telomerase-independent, alternative lengthening of telomeres (ALT) pathway, likely as a consequence of a telomere-based DNA damage response. Our results link the induction of TRF2 phosphorylation to the DNA damage-response system, providing an example of direct cross-talk via a signaling pathway between these two major cellular processes essential for genomic stability, telomere maintenance, and DNA repair.<\/jats:p>","DOI":"10.1073\/pnas.0507915102","type":"journal-article","created":{"date-parts":[[2005,10,13]],"date-time":"2005-10-13T20:33:29Z","timestamp":1129235609000},"page":"15539-15544","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":92,"title":["DNA damage-induced phosphorylation of the human telomere-associated protein TRF2"],"prefix":"10.1073","volume":"102","author":[{"given":"Hiromi","family":"Tanaka","sequence":"first","affiliation":[{"name":"Departments of Medical and Molecular Genetics, Radiation Oncology, and Medicine, Indiana University School of Medicine, Indianapolis, IN 46202; Program in Genetics and Genomic Biology, Research Institute, Hospital for Sick Children, Toronto, ON, Canada M5G 1X8; and Departments of Molecular and Medical Genetics and Pediatrics, University of Toronto, Toronto, ON, Canada M55 1A8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc S.","family":"Mendonca","sequence":"additional","affiliation":[{"name":"Departments of Medical and Molecular Genetics, Radiation Oncology, and Medicine, Indiana University School of Medicine, Indianapolis, IN 46202; Program in Genetics and Genomic Biology, Research Institute, Hospital for Sick Children, Toronto, ON, Canada M5G 1X8; and Departments of Molecular and Medical Genetics and Pediatrics, University of Toronto, Toronto, ON, Canada M55 1A8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul S.","family":"Bradshaw","sequence":"additional","affiliation":[{"name":"Departments of Medical and Molecular Genetics, Radiation Oncology, and Medicine, Indiana University School of Medicine, Indianapolis, IN 46202; Program in Genetics and Genomic Biology, Research Institute, Hospital for Sick Children, Toronto, ON, Canada M5G 1X8; and Departments of Molecular and Medical Genetics and Pediatrics, University of Toronto, Toronto, ON, Canada M55 1A8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek J.","family":"Hoelz","sequence":"additional","affiliation":[{"name":"Departments of Medical and Molecular Genetics, Radiation Oncology, and Medicine, Indiana University School of Medicine, Indianapolis, IN 46202; Program in Genetics and Genomic Biology, Research Institute, Hospital for Sick Children, Toronto, ON, Canada M5G 1X8; and Departments of Molecular and Medical Genetics and Pediatrics, University of Toronto, Toronto, ON, Canada M55 1A8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda H.","family":"Malkas","sequence":"additional","affiliation":[{"name":"Departments of Medical and Molecular Genetics, Radiation Oncology, and Medicine, Indiana University School of Medicine, Indianapolis, IN 46202; Program in Genetics and Genomic Biology, Research Institute, Hospital for Sick Children, Toronto, ON, Canada M5G 1X8; and Departments of Molecular and Medical Genetics and Pediatrics, University of Toronto, Toronto, ON, Canada M55 1A8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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