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Département Biologie des Génomes

par Clubs génome, EQYY - publié le , mis à jour le


  • 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>
    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

  • Vendredi 18 mai 11:00-12:00 - Klaas J. van Wijk - School for Integrative Plant Sciences, section of Plant Biology, Cornell University, Ithaca, NY, USA.

    Chloroplast Protein Homeostasis ; complexities of N-terminal protein maturation, the N-end rule and protease networks

    Résumé : Intra-chloroplast maturation and proteolysis is essential in biogenesis, differentiation and protein homeostasis (proteostasis). However, determinants of chloroplast protein life-time and protease-substrate relationships are poorly understood, even if this is of critical importance for plant life. Protein N-termini are major determinants of protein stability in bacteria, eukaryotes (the N-end rule), and perhaps also in chloroplasts. To better understand chloroplast protein maturation and stability, and to provide a base-line for protein degradation studies, we determined chloroplast protein N-termini using terminal amine isotopic labeling of substrates (TAILS) and mass spectrometry. This showed highly specific N-terminal patterns ; the possibility of a chloroplast N-end rule is discussed. The Clp protease system is the most complex and abundant protease in chloroplasts, and consists of a protease core, several chaperones and adaptors. Structural and functional features of the plastid Clp system in Arabidopsis thaliana will be illustrated though reverse genetics analysis combined with biochemical analysis, X-ray crystallography, as well as large scale quantitative proteomics for loss-of-function mutants. Multiple substrates were identified based on their direct interaction with the ClpS1 adaptor (N-recognin) or screening of different loss-of-function protease mutants ; we discuss the potential role of Clp in fine-tuning chloroplast metabolism. Finally, a chloroplast peptidase network based on co-expression analysis will be presented ; this will help elucidate chloroplast proteolysis cascades and substrate-protease relationships and is currently driving our chloroplast proteostasis research.
    Contact : Carmela GIGLIONE <carmela.giglione>

    Lieu : Auditorium - bâtiment 21 - Campus CNRS de Gif-sur-Yvette

    Notes de dernières minutes :

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