Article abstract
Nature Structural & Molecular Biology 14, 147 - 154 (2007)
Published online: 14 January 2007 | doi:10.1038/nsmb1192
A topological mechanism for TRF2-enhanced strand invasion
Simon Amiard1,2, Michel Doudeau2, Sébastien Pinte1, Anaïs Poulet1,3, Christelle Lenain1, Cendrine Faivre-Moskalenko3,4, Dimitar Angelov1,3, Nele Hug5, Alessandro Vindigni6, Philippe Bouvet1,3, Jacques Paoletti2, Eric Gilson1 & Marie-Josèphe Giraud-Panis1,3
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.
- Laboratoire de Biologie Moléculaire de la Cellule de l'Ecole Normale Supérieure de Lyon, CNRS UMR 5161, IFR128, 46 Allée d'Italie, 69364 Lyon Cedex 07, France.
- Centre de Biophysique Moléculaire, UPR301 CNRS, rue Charles Sadron, 45071 Orléans Cedex 2, France.
- Laboratoire Joliot Curie, Ecole Normale Supérieure, 46 Allée d'Italie, 69364 Lyon Cedex 07, France.
- Laboratoire de Physique, Ecole Normale Supérieure, 46 Allée d'Italie, 69364 Lyon Cedex 07, France.
- Swiss Institute for Experimental Cancer Research, Chemin des Boveresses 155, CH-1066 Epalinges s/Lausanne, Switzerland.
- International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34012 Trieste, Italy.
Correspondence to: Eric Gilson1 e-mail: eric.gilson@ens-lyon.fr
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