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4 mai 2018: 1 événement

  • Département Biologie des Génomes

    Vendredi 4 mai 11:00-12:00 - Sébastien Britton - Institut de Pharmacologie et de Biologie Structurale, CNRS and University of Toulouse, Toulouse, France

    Mechanisms antagonizing Ku at single-ended DNA double-strand breaks

    Résumé : Several anticancer agents, such as topoisomerase I poisons, induce single-ended DNA double-strand breaks (seDSBs). Owing to the absence of another DNA end suitable for direct ligation by the main DNA repair pathway Non-Homologous End Joining, seDSBs have to be repaired by Homologous Recombination (HR). HR is initiated by the generation of a 3’ overhang by exonuclease activities in a process called DNA end resection [1]. However, seDSBs are rapidly recognized by the DNA end binding protein Ku which shields them from exonuclease activities [2]. We have recently shown in human cells that a mechanism critical for cell survival releases Ku from seDSBs [2,3]. This mechanism relies on the creation of a nick by the CtIP-MRE11 complex on the flank of the break. This nick is an initiation site for DNA end resection and for the eviction of Ku, which is mediated at 40% of seDSBs by MRE11 exonuclease activity [3]. I will present our current progress on the characterization of this mechanism and its regulation by the ATM kinase.
    Contact : Julien BISCHEROUR <julien.bischerour i2bc.paris-saclay.fr>
    References :
    [1] Ciccia, Elledge. "The DNA damage response : making it safe to play with knives". Molecular cell (2010).
    [2] Britton S, Coates J, Jackson SP*. "A new method for high resolution imaging of Ku foci to decipher mechanisms of DNA double-strand break repair." Journal of Cell Biology (2013).
    [3] Chanut P†, Britton S†,*, Coates J, Jackson SP*, Calsou P*. "Coordinated nuclease activities antagonize Ku at single-ended DNA double-strand breaks." Nature communications (2016).

    Lieu : Salle des séminaires- bâtiment 26 - Campus CNRS de Gif-sur-Yvette

    En savoir plus : Département Biologie des Génomes