Objectif DNA double strand breaks (DSBs) and telomeres both represent ends of a linear chromosome, and both can lead to dangerous genomic rearrangements. Recent studies in budding yeast suggest that persistent DSBs associate with factors in two perinuclear compartments, at nuclear pores and in the inner nuclear membrane (INM). The stability of short telomeres also involves telomere binding to an INM protein, Mps3, and unequal sister chromatid exchange in the rDNA array is prevented by binding another INM protein, Heh1. In the absence of this anchor, rDNA rings are excised leading to premature senescence. From these studies it is clear that the interaction of chromatin with the nuclear periphery contributes to genome stability, yet many questions remain concerning the relocalization and its functional consequences. Are these interactions part of a common mechanism to stabilize or process breaks? Do they cross-talk with each other or do the anchorage sites provide distinct activities specific to the context of the DSB? This proposal will examine the role of nuclear pore and INM proteins in telomere maintenance, rDNA stability and DSB repair, but comparing the outcome of damage at the three sites in various mutant strains. I will use high resolution fluorescence imaging to observe the movement of a randomly distributed DSB to the INM or to pores, which can be distinguished by use of fluorescent tagging and a nup133 mutation. I will determine which repair pathways are regulated by the pores and by INM factors involved in perinuclear anchoring, and finally will investigate whether common mechanisms regulate DSBs processing and the repression of recombination at telomeres or within the rDNA. Intruiguingly all of the nuclear envelope components implicated in this process have homologues in higher eukaryotic cells, which suggests that these mechanisms may be conserved. Champ scientifique natural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticsmutationnatural sciencesbiological sciencesgeneticschromosomesnatural sciencesbiological sciencesgeneticsgenomes Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) FP7-PEOPLE-2009-IIF - Marie Curie Action: "International Incoming Fellowships" Appel à propositions FP7-PEOPLE-2009-IIF Voir d’autres projets de cet appel Régime de financement MC-IIF - International Incoming Fellowships (IIF) Coordinateur Novartis Forschungsstiftung Contribution de l’UE € 174 065,20 Adresse Maulbeerstrasse 66 4058 BASEL Suisse Voir sur la carte Type d’activité Research Organisations Contact administratif Dorothy Searles (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée