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Département Biologie des Génomes

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


  • Vendredi 28 février 10:00-11:00 - Tomio TAKAHASHI - Microbiology Department, I2BC

    Advances in understanding Topoisomerase I molecular mechanisms

    Résumé : Abstract :
    Chromosome structure and dynamics, DNA repair, DNA replication and transcription are all mechanisms that involve changes in the topology of DNA, requiring a set of enzyme called DNA topoisomerases. In particular, human topoisomerase IB (Top1) removes torsional stresses associated with DNA replication and transcription, and is important for the regulation of gene expression. Top1 activity involves one step of DNA cleavage and one step of DNA ligation. The current structural data suggests that Top1 clamps the DNA molecule during these two steps. However, there is little data concerning the mechanisms underlying the entry and the exit of the DNA molecule inside this toroidal structure.
    The topoisomerase IB from one hyperthermophilic archaeon, Caldiarchaeum subterraneum was recently found to be highly similar to the eukaryotic enzyme (1). This highly thermostable enzyme allowed me recently to solve the first structure of Top1 in an open conformation in the absence of DNA. This novel structure reveals that Top1 is a bimodular enzyme, in which one catalytic domain and one core domain are linked with one flexible hinge loop, which allows the opening/closing of the enzyme. Top1 dynamics raises question about the specificity of the enzyme towards specific DNA structures including supercoiled DNA and non-canonical DNA structures such as G-quadruplexes.
    I will also briefly introduce a new family of proteins, homologous with Topoisomerase IIB and Spo11, which are found exclusively in viruses (2).
    References :
    1. Dahmane N, Gadelle D, Delmas S, Criscuolo A, Eberhard S, Desnoues N, et al. TopIb, a phylogenetic hallmark gene of Thaumarchaeota encodes a functional eukaryote-like topoisomerase IB. Nucleic Acids Res. 2016 ;44(6):2795–805.
    2. Takahashi, T.S., Da Cunha, V., Krupovic, M., Mayer, C., Forterre, P., and Gadelle, D. Expanding the type IIB DNA topoisomerase family : identification of new topoisomerase and topoisomerase-like proteins in mobile genetic elements. NAR Genomics and Bioinformatics 2(1) (2020)
    Contact : Yoshi Yamaichi <Yoshiharu.YAMAICHI>

    Lieu : Bibliothèque- bâtiment 34 - Campus CNRS de Gif-sur-Yvette

  • Vendredi 6 mars 11:00-12:00 - David DULIN - IZNF – Interdisciplinary Center for Nanostructured Films, Erlangen, Germany

    Séminaire David DULIN

    Lieu : Salle A. Kalogeropoulos - bâtiment 400 - campus d'Orsay

  • Vendredi 13 mars 11:00-12:00 - Stefan HOFFMANN - University of Manchester, Royaume-Uni

    Continuous Culture in Directed Evolution Studies

    Résumé : Directed evolution is a powerful tool in protein engineering to achieve desired protein characteristics by selection, without requiring structural knowledge. Traditionally, in vivo selections are done in batch culture, which is characterised by a dynamically changing medium composition as cells multiply. This can make challenging selections difficult, especially dual selections for switchable function, due to affecting cell physiology and limited control over the selective stringency. To address this limitation, we have developed a continuous culture bioreactor system with optical feedback control and a volume-independent on-line estimation of growth rates. This small-scale turbidostat ( 20 ml) affords microbial cultures at freely chosen constant densities, enabling selections at steady physiological states with the capability of monitoring population fitness over time. It also facilitates longer selections typical for adaptive laboratory evolution experiments, with the growth rate assessment providing guidance for adjusting selective pressure.

    Contact : Christophe POSSOZ <Christophe.POSSOZ>

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

  • Vendredi 27 mars 11:00-12:00 - Sarah LAMBERT - Institut Curie, Orsay

    Resolution of replication stress in space and time for maintaining genome stability

    Résumé : Flaws in the DNA replication process, known as replication stress, result in inaccurate chromosome duplication and subsequent mitotic abnormalities Replication stress has emerged as a major source of genome instability contributing to genomic disorders, neurological diseases, aging and cancer. The causes of replication stress are many and varied but ultimately result in stressed replication forks that are fragile DNA structures prone to chromosomal rearrangements. The main research line of the team is to investigate the spatial and temporal organization of molecular circuits that prevent stressed forks to be converted into pathological DNA structures and the inheritance of DNA lesions and epi-genetic changes to the progeny. A combined genetic, biochemical and molecular approach allow us to explore how recombination, repair and chromatin-based processes resolve replication stress within the sub-nuclear architecture of the genome. This seminar will focus on our recent understanding of the role of the Nuclear Pore Complex (NPC) in promoting efficient restart of stressed replication forks. Several DNA lesions, such as persistent double-strand breaks, eroded telomeres and collapsed forks anchor to the NPC that acts as a docking site to facilitate DNA repair by elusive mechanisms. Using inducible replication fork barriers (RFBs) in fission yeast, we report that dysfunctional and double strand break-free replication forks relocate to the NPC after remodeling by Rad51 enzymatic activity. We reveal a novel function of the NPC in priming the step of recombination-dependent DNA synthesis, in a post-anchoring manner via the detoxification of SUMO conjugates. We found that the subsequent step of fork-restart by the homologous recombination pathway are spatially segregated : fork-resection and Rad51 activity occur within the core nucleus, followed by Ulp1-associated NPC being necessary to prime the DNA synthesis step, downstream Rad51 loading. We uncovered a novel spatio-temporal control of efficient fork-restart at unique sequence that is distinct from mechanisms engaged at collapsed-forks and breaks within repeated sequences.

    Contact : Mireille Bétermier <mireille.betermier>

    Lieu : Bibliothèque - bâtiment 34 - campus de Gif-sur-Yvette

  • Vendredi 20 mars - - I2BC

    Journée du département Biologie des Génomes

    Lieu : Auditorium - bâtiment 21 - campus de Gif-sur-Yvette

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