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  • 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>
      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 :


    • Vendredi 25 mai 11:00-12:00 - Emilie Brasset - GReD (Genetics, Reproduction and Development) Clermont Université, Clermont-Ferrand

      Transposable Element repression in the germline : piRNA as guardians of the genome integrity

      Résumé : Transposable elements (TEs) have the capacity to transpose and invade genomes. To ensure genome integrity for the next generation, their mobilization is strictly controlled in the germline. Extensive studies performed in Drosophila and mice have identified a special class of small RNAs called Piwi-interacting RNAs (piRNAs) that form a dedicated transposon silencing system to ensure germline genome integrity and fertility. Most of these piRNAs are produced from very special dedicated loci called piRNA clusters. Integration of transposons into piRNA clusters generates de novo piRNAs, which in turn exert trans-silencing activity against these transposons. It is not well understood yet how this piRNA clusters are defined and how their transcripts are taken in charge by the cell to produce piRNAs. Our project wishes to uncover underlying specificities of piRNA silencing in the germline and the involvement of this pathway in the transmission of the repression to the offspring using Drosophila as a model.
      Contact : Daan Noordermeer <daan.noordermeer>

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


  • I2BC

    • Mardi 22 mai 11:00-12:00 - Eric Espagne - Département Biologie des Génomes, I2BC

      Meiotic recombination and pairing

      Résumé : Meiosis is the specialized cellular program by which a diploid germline cell gives rise to haploid gametes for reproduction. Its successful execution includes recognition and pairing of homologous maternal and paternal chromosomes (homologs) and establishment of inter-homolog recombinational interactions (crossover/chiasmata) that create the physical linkages required for their correct segregation. Errors in segregation lead to extra or missing chromosomes in gametes (aneuploïdy), a major cause of human pregnancy failure and congenital disorders as well as sterility in plants. To understand the origin of aneuploïdies, we use the power of the fungus Sordaria for meiotic analysis by merging molecular, genetic and single cell direct visualization of chromosomes.
      Biochemical events of crossover (CO) formation occur in physical and functional linkage with chromosome axial structure from initiation through post-CO chiasma development. To understand this linkage, we developed two main approaches : (1) Investigation of the complex program of interactions between homologs that results in CO formation and installation of the specific pairing structure called « synaptonemal complex » (SC). (2) Analysis of why a CO event at one position on the chromosome hinders the occurrence of another CO nearby. This interesting “interference” process (Muller, 1906) requires communication along the chromosomes but its implementation and its evolutionary rationale remain unclear.

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


  • Virologie

    • Mercredi 30 mai 11:00-12:00 - Raphaël GAUDIN - Unité Interactions virus-hôtes et maladies hépatiques, INSERM, U1110, STRASBOURG, invité par Yves Gaudin

      Zika virus induces monocyte transmigration, spreading the infection to the brain

      Résumé : Zika virus (ZIKV) is an important public health concern worldwide since the major outbreaks observed in South and Central America. The most severe complications induced by ZIKV include fetal microcephaly in pregnant women, Guillain-Barré syndrome in adults, as well as other neurological disorders. Several reports showed that ZIKV establishes persistent infection in multiple tissues and body fluids such as in the brain, blood, saliva, urine and semen. The wide dissemination of the virus within the body implies that molecular and cellular mechanisms from the host are subverted to allow ZIKV virions to travel from their port of entry toward their final destination. How ZIKV disseminates from the blood-stream deep into the brain remains unclear. Here, we combined various approaches ranging from in vitro transwell assay, ex vivo organotypic culture, in vivo zebrafish model as well as analysis of samples from naturally infected patients. From our observations, we propose that ZIKV uses a Trojan horse strategy to disseminate into the brain through the help of blood-circulating monocytes.

      Lieu : Salle des séminaires - bâtiment 14C - Campus de Gif-sur-Yvette


  • Microbiologie

    • Mardi 29 mai 11:30-12:30 - Dr. Olivier Berteau - MICALIS, INRA, Jouys-en-Josas

      Radical SAM enzymes : Radically new reactions in natural product biosynthesis

      Résumé : Ribosomally-synthesized and post-translationally modified peptides (RiPPs) are a large and diverse family of natural products. They possess interesting biological properties such as antibiotic or anticancer activities, making them attractive for therapeutic applications. RiPPs are produced according to a simple biosynthetic logic, a precursor peptide containing a leader (or a follower) sequence is synthesized and modified to various extents by tailoring enzymes. The modified peptide is then generally secreted and the leader (or follower) cleaved off. RiPPs have been shown to contain a wealth of post-translational modifications such as thioether bonds, unusual methylations or epimerizations. In a unique manner, the so-called radical SAM enzymes, an emerging superfamily of metallo-enzymes have been shown to catalyze all these various and chemically unrelated modifications. I will present recent advances in our understanding of radical SAM enzymes and the post-translational modifications they catalyze.

      Lieu : Salle Kalogeropoulos, Bât 400, Université Paris sud - Campus Orsay


  • Club Bioinformatique

    • Lundi 28 mai 11:00-12:30 - Thomas Denecker - I2BC

      Club Bioinformatique, génomique et biologie des systèmes

      Résumé : Thomas Denecker (eq. BIM) :
      Etude du réseau de gènes impliqué dans le contrôle de l’homéostasie du fer de la levure C. glabrata

      Lieu : salle de conférence A.Kalogeropoulos - b.400, campus Orsay - Université Paris-Sud, 91405 - Orsay Cedex


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