Article
- The EMBO Journal (2009) 28, 641 - 651
- doi:10.1038/emboj.2009.11
Published online: 5 February 2009
Subject Category:
TRF2 promotes, remodels and protects telomeric Holliday junctions
Anaïs Poulet1,2,a, Rémi Buisson1,2,a, Cendrine Faivre-Moskalenko2,3, Mélanie Koelblen1, Simon Amiard1,2,b, Fabien Montel2,3, Santiago Cuesta-Lopez3, Olivier Bornet4, Françoise Guerlesquin4, Thomas Godet1,2, Julien Moukhtar2,3, Françoise Argoul2,3, Anne-Cécile Déclais5, David M J Lilley5, Stephen C Y Ip6, Stephen C West6, Eric Gilson1 and Marie-Josèphe Giraud-Panis1,2
- Université de Lyon, Laboratoire de Biologie Moléculaire de la Cellule, CNRS UMR5239, Ecole Normale Supérieure de Lyon, Lyon, France
- Université de Lyon, Laboratoire Joliot-Curie, CNRS USR3010, Ecole Normale Supérieure de Lyon, Lyon, France
- Université de Lyon, Laboratoire de Physique, CNRS UMR5672, Ecole Normale Supérieure de Lyon, Lyon, France
- Institut de Biologie Structurale et Microbiologie, CNRS, Marseille, France
- Cancer Research UK, Nucleic Acids Structure Research Group, MSI/WTB Complex, University of Dundee, Dundee, UK
- Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts, UK
Correspondence to:
Eric Gilson, Laboratoire de Biologie Moléculaire de la Cellule, Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon, France. Tel.: +33 472 728453; Fax: +33 472 728080; E-mail: Eric.Gilson@ens-lyon.fr
aThese authors contributed equally to this work
bPresent address: Université Clermont-Ferrand, UMR6247 CNRS, 24 av. des Landais, 61177 Aubière, France
Received 27 November 2008; Accepted 22 December 2008
Abstract
The ability of the telomeric DNA-binding protein, TRF2, to stimulate t-loop formation while preventing t-loop deletion is believed to be crucial to maintain telomere integrity in mammals. However, little is known on the molecular mechanisms behind these properties of TRF2. In this report, we show that TRF2 greatly increases the rate of Holliday junction (HJ) formation and blocks the cleavage by various types of HJ resolving activities, including the newly identified human GEN1 protein. By using potassium permanganate probing and differential scanning calorimetry, we reveal that the basic domain of TRF2 induces structural changes to the junction. We propose that TRF2 contributes to t-loop stabilisation by stimulating HJ formation and by preventing resolvase cleavage. These findings provide novel insights into the interplay between telomere protection and homologous recombination and suggest a general model in which TRF2 maintains telomere integrity by controlling the turnover of HJ at t-loops and at regressed replication forks.
Keywords:
- recombination,
- resolvase,
- telomere,
- TRF2
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