Benarroch-Popivker, DelphinePisano, SabrinaMendez-Bermudez, AaronLototska, LiudmylaKaur, ParminderBauwens, SergeDjerbi, NadirLatrick, Chrysa M.Fraisier, VincentPei, BeiGay, AlexandreJaune, EmilieFoucher, KevinCherfils-Vicini, JulienAeby, EricMiron, SimonaLondono-Vallejo, ArturoYe, JingLe Du, Marie-HeleneWang, HongGilson, EricGiraud-Panis, Marie-Josephe2016-07-192016-07-192016-07-19201610.1016/j.molcel.2015.12.009https://infoscience.epfl.ch/handle/20.500.14299/127922WOS:000372325400010The 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 similar to 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.text::journal::journal article::research article