A topological mechanism for TRF2-enhanced strand invasion.
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.
Amiard
Simon
S
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.
Doudeau
Michel
M
Pinte
Sébastien
S
Poulet
Anaïs
A
Lenain
Christelle
C
Faivre-Moskalenko
Cendrine
C
Angelov
Dimitar
D
Hug
Nele
N
Vindigni
Alessandro
A
Bouvet
Philippe
P
Paoletti
Jacques
J
Gilson
Eric
E
Giraud-Panis
Marie-Josèphe
MJ
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*
D004278:DNA, Superhelical; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; D004247:DNA