Recruitment of TRF2 to laser-induced DNA damage sites

Nazmul Huda, Satoshi Abe, Ling Gu, Marc S. Mendonca, Samarendra Mohanty, David Gilley

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Several lines of evidence suggest that the telomere-associated protein TRF2 plays critical roles in the DNA damage response. TRF2 is rapidly and transiently phosphorylated by an ATM-dependent pathway in response to DNA damage and this DNA damage-induced phosphoryation is essential for the DNA-PK-dependent pathway of DNA double-strand break repair (DSB). However, the type of DNA damage that induces TRF2 localization to the damage sites, the requirement for DNA damage-induced phosphorylation of TRF2 for its recruitment, as well as the detailed kinetics of TRF2 accumulation at DNA damage sites have not been fully investigated. In order to address these questions, we used an ultrafast femtosecond multiphoton laser and a continuous wave 405-nm single photon laser to induce DNA damage at defined nuclear locations. Our results showed that DNA damage produced by a femtosecond multiphoton laser was sufficient for localization of TRF2 to these DNA damage sites. We also demonstrate that ectopically expressed TRF2 was recruited to DNA lesions created by a 405-nm laser. Our data suggest that ATM and DNA-PKcs kinases are not required for TRF2 localization to DNA damage sites. Furthermore, we found that phosphorylation of TRF2 at residue T188 was not essential for its recruitment to laser-induced DNA damage sites. Thus, we provide further evidence that a protein known to function in telomere maintenance, TRF2, is recruited to sites of DNA damage and plays critical roles in the DNA damage response.

Original languageEnglish (US)
Pages (from-to)1192-1197
Number of pages6
JournalFree Radical Biology and Medicine
Volume53
Issue number5
DOIs
StatePublished - Sep 1 2012

Keywords

  • DNA damage response
  • Laser microirradiation
  • Phosphorylation
  • Telomere
  • TRF2

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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