TRF2 promotes, remodels and protects telomeric Holliday junctions

Anais Poulet, Remi Buisson, Cendrine Faivre-Moskalenko, Melanie Koelblen, Simon Amiard, Fabien Montel, Santiago Cuesta-Lopez, Olivier Bornet, Francoise Guerlesquin, Thomas Godet, Julien Moukhtar, Francoise Argoul, Anne-Cecile Declais, David M. J. Lilley, Stephen C. Y. Ip, Stephen C. West, Eric Gilson, Marie-Josephe Giraud-Panis

    Research output: Contribution to journalArticlepeer-review

    98 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)641-651
    Number of pages11
    JournalEMBO Journal
    Volume28
    Issue number6
    DOIs
    Publication statusPublished - 18 Mar 2009

    Keywords

    • recombination
    • resolvase
    • telomere
    • TRF2
    • TOPOISOMERASE-III-ALPHA
    • BRANCH MIGRATION
    • HOMOLOGOUS RECOMBINATION
    • RESOLVING ENZYME
    • STRUCTURAL RECOGNITION
    • ENDONUCLEASE-VII
    • DNA JUNCTION
    • IN-VITRO
    • BINDING
    • REPLICATION

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