Obiettivo Our cells are faced with thousands of DNA lesions every day. Failure to repair such lesions can lead to genomic instability, cancer development or cell death. Repair of DNA damage, however, is complicated by the fact that genomic DNA is packaged, through histone and non-histone proteins, into a condensed structure called chromatin. Recently, an increasing interest on the impact of chromatin and the epigenetic changes that occur in DNA damage repair has emerged. Nevertheless, the functional interplay between damage-induced interference of transcription and modulation of chromatin to allow accessibility of DNA lesions by the repair machineries is still an enigma. Here, I propose biochemical and genetic approaches complemented with advanced proteomic and genome wide technologies to i) isolate and characterise the chromatin remodelling factors that functionally interact with damage arrested RNA Polymerase II/repair complexes in response to genotoxic stress. Focus will be on potential differences in the composition of protein complexes and their posttranslational modifications in normal human cells and in patient-derived repair deficient cells. ii) To decode the epigenetic changes that occur in response to DNA damage at genome wide level and in the vicinity of transcription blocking DNA lesions. iii) To elucidate the role of key repair and chromatin factors on transcription-mediated DNA damage response and study their interplay with damage signaling proteins (such as protein kinases, ubiquitin ligases, and histone methylases/acetyltransferases).These studies are expected to increase our understanding on the impact of chromatin function-structure and the histone modifications that occur upon genotoxic stress and change transiently the plasticity of chromatin structure, linking persistent damage in active genes to repair, cell cycle arrest or apoptosis in mammalian cells. In addition, this knowledge may lead to the identification of targets for therapeutic intervention. Campo scientifico natural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticsgenomesnatural sciencesbiological sciencesgeneticsepigenetics Programma(i) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) FP7-PEOPLE-2009-IEF - Marie Curie Action: "Intra-European Fellowships for Career Development" Invito a presentare proposte FP7-PEOPLE-2009-IEF Vedi altri progetti per questo bando Meccanismo di finanziamento MC-IEF - Intra-European Fellowships (IEF) Coordinatore EREVNITIKO KENTRO VIOIATRIKON EPISTIMON ALEXANDROS FLEMINGK Contributo UE € 202 318,80 Indirizzo FLEMING STREET 34 16672 Vari-Athens Grecia Mostra sulla mappa Regione Αττική Aττική Ανατολική Αττική Tipo di attività Research Organisations Contatto amministrativo Elsa Rokofyllou (Ms.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato