TY - JOUR
T1 - A topological mechanism for TRF2-enhanced strand invasion
AU - Amiard, Simon
AU - Doudeau, Michel
AU - Pinte, Sébastien
AU - Poulet, Anaïs
AU - Lenain, Christelle
AU - Faivre-Moskalenko, Cendrine
AU - Angelov, Dimitar
AU - Hug, Nele
AU - Vindigni, Alessandro
AU - Bouvet, Philippe
AU - Paoletti, Jacques
AU - Gilson, Eric
AU - Giraud-Panis, Marie Josèphe
N1 - Funding Information:
We thank R. Rahmouni for advice. This work was supported by grants from the Ligue Nationale contre le Cancer (‘‘équipe labellisée’’) and from ‘‘Région Centre’’. C.L. is supported by fellowships from the Association pour la Recherche sur le Cancer.
PY - 2007/2
Y1 - 2007/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33846969882&partnerID=8YFLogxK
U2 - 10.1038/nsmb1192
DO - 10.1038/nsmb1192
M3 - Article
C2 - 17220898
AN - SCOPUS:33846969882
SN - 1545-9993
VL - 14
SP - 147
EP - 154
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 2
ER -