TRF2 is required for repair of nontelomeric DNA double-strand breaks by homologous recombination
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Edited by Fred Sherman, University of Rochester Medical Center, Rochester, NY, and approved June 25, 2007 (received for review March 14, 2007)
Abstract
TRF2 (telomeric repeat binding factor 2) is an essential component of the telomeric cap, where it forms and stabilizes the T-loop junctions. TRF2 forms the T-loops by stimulating strand invasion of the 3′ overhang into duplex DNA. TRF2 also has been shown to localize to nontelomeric DNA double-strand breaks, but its functional role in DNA repair has not been examined. Here, we present evidence that TRF2 is involved in homologous recombination (HR) repair of nontelomeric double-strand breaks. Depletion of TRF2 strongly inhibited HR and delayed the formation of Rad51 foci after γ-irradiation, whereas overexpression of TRF2 stimulated HR. Depletion of TRF2 had no effect on nonhomologous end-joining, and overexpression of TRF2 inhibited nonhomologous end-joining. We propose, based on our results and on the ability of TRF2 to mediate strand invasion, that TRF2 plays an essential role in HR by facilitating the formation of early recombination intermediates.
Footnotes
- *To whom correspondence may be addressed: University of Rochester, 213 Hutchison Hall, River Campus, Rochester, NY 14627-0211. E-mail: vgorbuno{at}mail.rochester.edu
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Author contributions: Z.M., A.S., and V.G. designed research; Z.M., A.S., and Y.J. performed research; Z.M., A.S., and V.G. analyzed data; and V.G. wrote the paper.
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The authors declare no conflict of interest.
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This article is a PNAS Direct Submission.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0702410104/DC1.
- Abbreviations:
- DSB,
- double-strand break;
- HR,
- homologous recombination;
- NHEJ,
- nonhomologous end-joining;
- HPRT,
- hypoxanthine phosphoribosyltransferase;
- hTERT,
- human telomerase reverse transcriptase.
- © 2007 by The National Academy of Sciences of the USA
