Objetivo The eukaryotic genome is packaged into large-scale chromatin structures occupying distinct domains in the cell nucleus. Nuclear compartmentalization has recently been proposed to play an important role in genome stability but the molecular steps regulated remain to be defined. Focusing on Double strand breaks (DSBs) in response to which cells activate checkpoint and DNA repair pathways, we propose to characterize the spatial and temporal behavior of damaged chromatin and determine how this affects the maintenance of genome integrity. Currently, most studies concerning DSBs signaling and repair have been realized on asynchronous cell populations, which makes it difficult to precisely define the kinetics of events that occur at the cellular level. We thus propose to follow the nuclear localization and dynamics of an inducible DSB concomitantly with the kinetics of checkpoint activation and DNA repair at a single cell level and along the cell cycle. This will be performed using budding yeast as a model system enabling the combination of genetics, molecular biology and advanced live microscopy. We recently demonstrated that DSBs relocated to the nuclear periphery where they contact nuclear pores. This change in localization possibly regulates the choice of the repair pathway through steps that are controlled by post-translational modifications. This proposal aims at dissecting the molecular pathways defining the position of DSBs in the nucleus by performing genetic and proteomic screens, testing the functional consequence of nuclear position for checkpoint activation and DNA repair by driving the DSB to specific nuclear landmarks and, defining the dynamics of DNA damages in different repair contexts. Our project will identify new players in the DNA repair and checkpoint pathways and further our understanding of how the compartmentalization of damaged chromatin into the nucleus regulates these processes to insure the transmission of a stable genome. Ámbito científico natural sciencesbiological sciencesgeneticsDNAnatural sciencesphysical sciencesopticsmicroscopynatural sciencesbiological sciencesmolecular biologynatural sciencesbiological sciencesgeneticsgenomeseukaryotic genomes Programa(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Tema(s) ERC-SG-LS1 - ERC Starting Grant - Molecular and Structural Biology and Biochemistry Convocatoria de propuestas ERC-2011-StG_20101109 Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-SG - ERC Starting Grant Institución de acogida COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES Aportación de la UE € 1 499 863,00 Dirección RUE LEBLANC 25 75015 PARIS 15 Francia Ver en el mapa Región Ile-de-France Ile-de-France Paris Tipo de actividad Research Organisations Contacto administrativo Olivier Leroy (Mr.) Investigador principal Karine Marie Renée Dubrana (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos Beneficiarios (1) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES Francia Aportación de la UE € 1 499 863,00 Dirección RUE LEBLANC 25 75015 PARIS 15 Ver en el mapa Región Ile-de-France Ile-de-France Paris Tipo de actividad Research Organisations Contacto administrativo Olivier Leroy (Mr.) Investigador principal Karine Marie Renée Dubrana (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos
