Objetivo The DNA within our cells is constantly being damaged by both environmental and endogenous agents; of the many forms of DNA damage, the DNA double-strand break (DSB) is considered to be most dangerous. Correct processing of DSBs is not only essential for maintaining genomic integrity but is also required in specific biological processes, such as meiotic recombination and V(D)J recombination, in which DNA breaks are deliberately generated. In animals, defects in the proper response to DSBs can thus have different outcomes: cancer predisposition, embryonic lethality, or compromised immunity. Many genes that play a role in the processing of DSBs have been identified over the past decades, mainly by cloning genes that are responsible for specific human genomic instability or immune deficiency syndromes, and by genetic approaches using unicellular eukaryotes and rodent cell lines. It is, however, evident that many components required in higher eukaryotes are not yet known and the identification of those will be a major challenge for future research. Here, we will for the first time systematically test all genes encoded by an animals genome directly for their involvement in the cellular response to DSB in both somatic and germline tissues: we will use our recently developed transgenic animal models (C. elegans) that visualizes repair of a single localized genomic DNA break in genome wide RNAi screenings to identify (and then characterize) the complement of genes that are required to keep our genome stable, and when mutated can predispose humans to cancer. In parallel, we will study the cellular response to single DNA breaks that are artificially generated during different stages of gametogenesis, as well as address the developmental consequences of DSB induction during the earliest stages of embryonic development – an almost completely unexplored area in the field of genome instability and DNA damage responses. Ámbito científico natural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesdevelopmental biologymedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticsgenomes Palabras clave DNA damage responses DNA double-strand breaks Genomic instability 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-LS2 - ERC Starting Grant - Genetics,Genomics,Bioinformatics and Systems Biology Convocatoria de propuestas ERC-2007-StG Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-SG - ERC Starting Grant Institución de acogida ACADEMISCH ZIEKENHUIS LEIDEN Aportación de la UE € 1 022 269,55 Dirección ALBINUSDREEF 2 2333 ZA Leiden Países Bajos Ver en el mapa Región West-Nederland Zuid-Holland Agglomeratie Leiden en Bollenstreek Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Liesbeth Dorama (Ms.) Investigador principal Marcel Tijsterman (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos Beneficiarios (2) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo ACADEMISCH ZIEKENHUIS LEIDEN Países Bajos Aportación de la UE € 1 022 269,55 Dirección ALBINUSDREEF 2 2333 ZA Leiden Ver en el mapa Región West-Nederland Zuid-Holland Agglomeratie Leiden en Bollenstreek Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Liesbeth Dorama (Ms.) Investigador principal Marcel Tijsterman (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW La participación finalizó Países Bajos Aportación de la UE € 37 730,45 Dirección KLOVENIERSBURGWAL 29 HET TRIPPENHUIS 1011 JV AMSTERDAM Ver en el mapa Región West-Nederland Noord-Holland Groot-Amsterdam Tipo de actividad Research Organisations Contacto administrativo Don Van Velzen (Mr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos
