A topological mechanism for TRF2-enhanced strand invasion

Simon Amiard, Michel Doudeau, Sébastien Pinte, Anaïs Poulet, Christelle Lenain, Cendrine Faivre-Moskalenko, Dimitar Angelov, Nele Hug, Alessandro Vindigni, Philippe Bouvet, Jacques Paoletti, Eric Gilson, Marie Josèphe Giraud-Panis

Research output: Contribution to journalArticlepeer-review

137 Scopus citations

Abstract

Telomeres can fold into t-loops that may result from the invasion of the 3′ overhang into duplex DNA. Their formation is facilitated in vitro by the telomeric protein TRF2, but very little is known regarding the mechanisms involved. Here we reveal that TRF2 generates positive supercoiling and condenses DNA. Using a variety of TRF2 mutants, we demonstrate a strong correlation between this topological activity and the ability to stimulate strand invasion. We also report that these properties require the combination of the TRF-homology (TRFH) domain of TRF2 with either its N- or C-terminal DNA-binding domains. We propose that TRF2 complexes, by constraining DNA around themselves in a right-handed conformation, can induce untwisting of the neighboring DNA, thereby favoring strand invasion. Implications of this topological model in t-loop formation and telomere homeostasis are discussed.

Original languageEnglish
Pages (from-to)147-154
Number of pages8
JournalNature Structural and Molecular Biology
Volume14
Issue number2
DOIs
StatePublished - Feb 2007

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