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TRF2-Mediated Control of Telomere DNA Topology as a Mechanism for Chromosome-End Protection.

Authors: Delphine D. Benarroch-Popivker, Sabrina S. Pisano, Aaron A. Mendez-Bermudez, Liudmyla L. Lototska, Parminder P. Kaur, Serge S. Bauwens, Nadir N. Djerbi, Chrysa M CM. Latrick, Vincent V. Fraisier, Bei B. Pei, Alexandre A. Gay, Emilie E. Jaune, Kevin K. Foucher, Julien J. Cherfils-Vicini, Eric E. Aeby, Simona S. Miron, Arturo A. Londoño-Vallejo, Jing J. Ye, Marie-Hélène MH. Le Du, Hong H. Wang, Eric E. Gilson, Marie-Josèphe MJ. Giraud-Panis
Published: 01/07/2016, Molecular cell


The shelterin proteins protect telomeres against activation of the DNA damage checkpoints and recombinational repair. We show here that a dimer of the shelterin subunit TRF2 wraps ∼90 bp of DNA through several lysine and arginine residues localized around its homodimerization domain. The expression of a wrapping-deficient TRF2 mutant, named Top-less, alters telomeric DNA topology, decreases the number of terminal loops (t-loops), and triggers the ATM checkpoint, while still protecting telomeres against non-homologous end joining (NHEJ). In Top-less cells, the protection against NHEJ is alleviated if the expression of the TRF2-interacting protein RAP1 is reduced. We conclude that a distinctive topological state of telomeric DNA, controlled by the TRF2-dependent DNA wrapping and linked to t-loop formation, inhibits both ATM activation and NHEJ. The presence of RAP1 at telomeres appears as a backup mechanism to prevent NHEJ when topology-mediated telomere protection is impaired.

Copyright © 2016 Elsevier Inc. All rights reserved.
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