Obiettivo Understanding how the genetic information of a cell is retrieved but also protected from insults, is a major challenge facing modern molecular biology. Indeed, one of the most important developments in human genetics over the last decade, has been the realization that diseases such as cancer but also ageing stem from some dis-regulation in the expression and preservation of the genetic information. TFIIH is a multiprotein complex that is essential in transcription and DNA repair. Mutations in some of its subunits are responsible of a UV sensitivity phenotype in yeast and drosophila. In human, this results in the rare DNA repair deficient genetic disorder, xeroderma pigmentosum (XP), which is characterized by photosensitivity and an increased risk of skin cancers. Two further disorders involving mutation in TFIIH subunits, Cockayne syndrome (CS) and trichothiodystrophy (TTD) are also defective in repair of UV damage, but present quite different clinical features such as brittle hair, neurological and developmental retardation, middles sun sensitivity and no susceptibility to solar carcinogenesis. The clinical complexity of these syndromes cannot be explained solely by deficiencies in DNA repair and emerging evidences indicate that it may also result from a dys-regulation of the transcriptional program under the control of hormones. The goal of this proposal is to investigate the DNA repair/transcription disorders involving mutations in TFIIH. This research will not only assists afflicted XP, CS, TTD and normal individuals in prevention and ultimately cures of hormonal dependent diseases and cancer (the clinical point of view), but more generally will provide an improved understanding of the mechanisms that regulate the expression of protein coding genes and the maintenance of genome integrity (the fundamental research point of view). Campo scientifico medical and health sciencesclinical medicineoncologyskin cancernatural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesbasic medicinemedical geneticsnatural sciencesbiological sciencesgeneticsgenomes Parole chiave Nucleotide excision repair TFIIH genome integrity mRNA transcription Programma(i) 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) Argomento(i) ERC-AG-LS1 - ERC Advanced Grant - Molecular and Structural Biology and Biochemistry Invito a presentare proposte ERC-2008-AdG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-AG - ERC Advanced Grant Istituzione ospitante CENTRE EUROPEEN DE RECHERCHE EN BIOLOGIE ET MEDECINE Contributo UE € 1 997 000,00 Indirizzo Rue Laurent Fries 1 67404 Illkirch Graffenstaden Francia Mostra sulla mappa Regione Grand Est Alsace Bas-Rhin Tipo di attività Research Organisations Contatto amministrativo Steve Brooks (Dr.) Ricercatore principale Jean-Marc Egly (Prof.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto CENTRE EUROPEEN DE RECHERCHE EN BIOLOGIE ET MEDECINE Francia Contributo UE € 1 997 000,00 Indirizzo Rue Laurent Fries 1 67404 Illkirch Graffenstaden Mostra sulla mappa Regione Grand Est Alsace Bas-Rhin Tipo di attività Research Organisations Contatto amministrativo Steve Brooks (Dr.) Ricercatore principale Jean-Marc Egly (Prof.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato