title: A topological mechanism for TRF2-enhanced strand invasion.
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.
authors.affiliation: 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.
authors.forename: Simon
authors.initials: S
authors.lastname: Amiard
authors.forename: Michel
authors.initials: M
authors.lastname: Doudeau
authors.forename: Sébastien
authors.initials: S
authors.lastname: Pinte
authors.forename: Anaïs
authors.initials: A
authors.lastname: Poulet
authors.forename: Christelle
authors.initials: C
authors.lastname: Lenain
authors.forename: Cendrine
authors.initials: C
authors.lastname: Faivre-Moskalenko
authors.forename: Dimitar
authors.initials: D
authors.lastname: Angelov
authors.forename: Nele
authors.initials: N
authors.lastname: Hug
authors.forename: Alessandro
authors.initials: A
authors.lastname: Vindigni
authors.forename: Philippe
authors.initials: P
authors.lastname: Bouvet
authors.forename: Jacques
authors.initials: J
authors.lastname: Paoletti
authors.forename: Eric
authors.initials: E
authors.lastname: Gilson
authors.forename: Marie-Josèphe
authors.initials: MJ
authors.lastname: Giraud-Panis
mesh_terms: D004247:DNA / Q000737:chemistry*; D004278:DNA, Superhelical / Q000737:chemistry; D006801:Humans; D018625:Microscopy, Atomic Force; D009690:Nucleic Acid Conformation; D016615:Telomere / Q000737:chemistry*; D035321:Telomeric Repeat Binding Protein 1 / Q000737:chemistry; D035341:Telomeric Repeat Binding Protein 2 / Q000737:chemistry*
chemical_list: D004278:DNA, Superhelical; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; D004247:DNA