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  • Génomes

    • Vendredi 2 février 11:00-12:00 - Anne Royou - Institut de Biochimie et Génétique Cellularies, Université de Bordeaux

      How are broken chromosomes processed and faithfully transmitted to daughter cells

      Résumé : During interphase, DNA lesions such as double strand breaks (DSB) trigger a signalling pathway called the DNA damage response (DDR) that repairs the damage while concomitantly delaying cell cycle progression. Recent studies have shown that in the presence of DSBs during mitosis, the early steps of the DDR are activated while the downstream repair pathways are inhibited. It is thought that these DNA damage sensors mark the DSBs to allow their efficient repair in the next G1 phase. However, how mitotic cells preserve faithful transmission of broken chromosome fragments while processing DSBs is not understood. We have recently identified a mechanism by which broken chromosomes are faithfully transmitted to daughter cells via the tethering of the two broken chromosome ends. This mechanism involves several mitotic proteins, including BubR1, Bub3 and Polo, which are best known for their role in monitoring the proper attachment of chromosomes to the spindle microtubules. I will present our recent findings that address how BubR1, Bub3 and Polo are recruited to DNA breaks in mitosis and address their relationship to components of the DNA damage response.
      Contact : Laure CRABBE <Laure.CRABBE i2bc.paris-saclay.fr>

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

      Article

    • Mardi 20 février 11:00-12:30 - Ali Hamiche - IGBMC-Illkirch

      Towards a comprehensive view of the epigenetic landscape

      Résumé : Histone variants are essential epigenetic players implicated in key nuclear events. However, their role in transcription regulation and genome organization is not clear and much remains to be done to understand their function in these processes. A key question for understanding their functional and structural involvement in all these roles is whether their location through chromatin is random or not, and if not, how are the specific sites of deposition determined and regulated ? The purpose of this presentation is to provide a comprehensive view about the genome-wide pattern of histone variants distribution in relation to DNA methylation and to their potential role in promoter architecture organization and transcription regulation.

      Lieu : salle de conférence du Bât. 144 - Bât. 144
      Campus CEA/Saclay

      Article

  • Biologie Cellulaire

    • Vendredi 2 février 11:00-12:00 - François PARCY - Institut de Biosciences et Biotechnologies de Grenoble (BIG), invité par Grégory Vert

      A structural journey among floral regulators

      Résumé : In Arabidopsis like in many other plants, the development of flowers starts on the flanks of the shoot apical meristem. The position of the floral meristem is determined by the phytohormone auxin and the Auxin Response Factor Monopteros/ARF5 protein. Soon afterwards, the LEAFY transcription factor contributes to the emergence and the floral fate of the newly formed flower meristem. I will present how the combination of molecular genetics, epigenetics, structural biology, genomics and modeling allows to better understand the basic properties of these transcription factors and their function during flower development.

      Lieu : Auditorium - bâtiment 21 - campus de Gif

      Article

    • Vendredi 16 février 11:00-12:30 - Mireille MONTCOUQUIOL - INSERM Bordeaux, invitée par Anne-Marie Tassin

      Identification of a common molecular mechanism leading to hearing deficit and corpus callosum agenesis

      Résumé : The Chudley McCullough syndrome (CMCS) is a rare autosomal recessive neurological disorder characterized by early and severe onset of deafness and brain anomalies (Chudley et al., 1997). Mutations in the G protein signaling modulator 2 (GPSM2) gene were found to be causative of this pathology (Shahin et al., 2010 ; Walsh et al., 2010 ; Doherty et al., 2012) but the molecular and cellular bases of this pathology is unknown.
      Here, we show that Gpsm2 and Gαi3 proteins define a nanodomain (STED microscopy) at the tips of the tallest stereocilia in auditory cells and that this localization requires the presence of myosin 15 and whirlin, well-known regulators of stereocilia elongation. In absence of Gpsm2 the stereocilia elongation process is stopped, leading to a shortening of the hair bundle representing the most probable cause for early and severe deafness in the CMCS patients and in our mouse model. We further report that absence of Gnai3 leads to elevated hearing threshold, correlating with hair bundle elongation defects confined to high-frequency cochlear regions.
      Mechanistically, we identify an interaction between Gpsm2 and whirlin, and we show that this interaction affects the ability of the myosin 15/whirlin complex to generate filopodia in heterologous cells. Because filopodia (like stereocilia) elongation depends on actin polymerization, we further demonstrate that Gpsm2 mutations lead to a reduction in F-actin levels while overexpression of the Gpsm2/Gαi3 complex increases F-actin levels. Our data support the idea that Gpsm2/Gαi3 complex is at the interface between the actin and the membrane to regulate the actin polymerization at the tip of stereocilia or filopodia.
      We speculated that a similar actin-dependent post-mitotic mechanism could cause one of the brain abnormalities observed in patients, an hypoplasia of the corpus callosum and hippocampal commissures. Using Stp-PALM we show that the outgrowth of hippocampal young neurons is indeed reduced in Gpsm2 mutants, and we correlated this reduction with a deficit of actin dynamics, which could explain the defect of the corpus callosum.
      Altogether, our study 1/ identify the cause of the deafness in CMCS patients, 2/ identify a new molecular function for Gpsm2 in the regulation of actin dynamics, and 3/ suggest a post-mitotic cause for one of the central nervous system syndromes observed in patients.

      Lieu : Bibliothèque - bâtiment 34 - Campus de Gif-sur-yvette

      Article

    • Vendredi 23 février 11:00-12:00 - Mikael MOLIN - Department of Chemistry & Molecular Biology, University of Gothenburg, Göteborg, Sweden, invité par Benoît D'AUTREAUX

      Hydrogen peroxide-stimulated longevity - or why light and caloric restriction may extend your life

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

      Article

  • I2BC

    • Lundi 19 février 11:30-13:00 - Pierre Gonczy - Ecole Polytechnique Fédérale de Lausanne, Suisse

      Mechanisms of centriole assembly

      Résumé : The centriole is a remarkable microtubule-based organelle that is essential for the formation of cilia, flagella and centrosomes. The centriole is organized around a nine-fold symmetrical cartwheel typically 100 nm in height, which is critical for the onset of organelle biogenesis. The cartwheel comprises a stack of ring-containing entities that each accommodates nine homodimers of SAS-6 proteins. In contrast to the knowledge about the self-assembly properties of SAS-6 proteins, the mechanisms enabling ring stacking are poorly understood. Furthermore, the assembly dynamics of SAS-6 ring-containing entities remains elusive.
      After introducing the subject matter, I will report notably on our development of a cell-free assay to address this important open question using the Chlamydomonas reinhardtii SAS-6 protein CrSAS-6. Using high-speed atomic force microscopy (AFM), we monitored the assembly dynamics of CrSAS-6 homodimers, and thus determined possible routes and kinetic rates for CrSAS-6 ring formation.


      Invité par Anne-Marie Tassin, équipe Biogénese et fonction des structures centriolaires et ciliaires

      Lieu : Auditorium I2BC - Bâtiment 21
      Campus CNRS de Gif-sur-Yvette

      Article

  • B3S

    • Vendredi 16 février 14:00-15:30 - Pr Christine Ziegler - University of Regensburg, Germany

      Na+ coupling and K+ regulation in the secondary betaine transporter BetP

      Lieu : Auditorium I2BC - Bâtiment 21 - Campus de Gif-sur-Yvette

      Article

  • cytoskeleton club

    • Mardi 13 février 11:30-12:30 - Louis Renault

      Cytoskeleton club

      Résumé : How ExoY-Like bacterial nucleotidyl cyclase toxins from Pseudomonas aeruginosa and Vibrio nigripulchritudo are activated in host cells ?

      Lieu : Bibliothèque - Bâtiment 34, campus de Gif

      Article

Soutenance

  • B3S

    • Vendredi 16 février 10:00-12:30 - José Luis Vazquez-Ibar - Laboratoire des Protéines et Systèmes Membranaires, Département B3S, I2BC

      Structural and functional studies of membrane transport proteins

      Lieu : Auditorium I2BC - Bâtiment 21 - Campus de Gif-sur-Yvette

      Article

    • Vendredi 23 février 14:00-18:25 - Danni LIU - Equipe OCHSENBEIN, I2BC

      Rôle des chaperons d’histones dans la réplication et réparation de l’ADN

      Résumé : La chromatine chez les eucaryotes, porte des informations génétiques et épigénétiques. Les mécanismes garantissant le maintien de ces informations lors de la division cellulaire ou la réparation de l’ADN sont encore mal connus et ils constituent l’enjeu principal du projet de thèse. Plus particulièrement, l’objectif du projet de thèse est de chercher à comprendre comment les chaperons d’histones coordonnent leur action avec des partenaires associés à la fourche de réplication pour conserver les marques épigénétiques portées par les histones parentales et les reporter sur les histones nouvellement synthétisées. Cette thèse décrit précisément comment ASF1 (Anti Silencing Function 1) coopère avec le complexe CAF-1 (Chromatin Assembly Factor 1) et la sous-unité de l’hélicase réplicative MCM2 (Mini Chromosome Maintenance 2), pour la prise en charge des H3-H4 dans la réplication et la réparation de l’ADN. La thèse s’intéresse également à la régulation de l’activité de ces chaperons d’histones par des kinases activées suite à des stress réplicatifs ou des dommages de l’ADN. En particulier nous avons cherché à mieux comprendre comment l’ajout de groupements phosphate sur ASF1 par une enzyme appelée TLK (Tousled Like Kinase) module son activité au cours du cycle cellulaire et en réponse aux dommages de l’ADN. La caractérisation de l’importance des sites phosphorylés sur les propriétés de liaison du chaperon, permet de mieux comprendre le rôle joué par différent forme d’ASF1 dans l’assemblage des histones sur l’ADN et le maintien des informations épigénétiques. Le travail de thèse contient d’analyses biochimiques et structurales par une combinaison de techniques (SEC-MALS, AUC, ITC, RMN, cristallographie des rayons X) et d’analyses fonctionnelles sur des modèles cellulaires.

      Lieu : Amphithéatre Bloch, rez de chaussée Bât.772 - lieu-dit L’Orme des Merisiers
      Route de l’Orme
      91190 Saint-Aubin.

      Article

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