Obiettivo Linear chromosomes of eukaryotes end with telomeres that ensure their stability. Because of the inability of semi-conservative DNA replication machinery to fully replicate DNA ends, telomeres require dedicated mechanisms to be duplicated and their length is eroded at each cell division. For this reason, telomeres constitute molecular clocks that determine cell proliferation potential in eukaryotes. Strikingly, we have shown recently that it is the shortest telomere in the cell that determines the onset of replicative senescence. This project aims a complete and detailed dissection of the in vivo DNA-end replication problem and the deep understanding of its impact for cell division capability. Specifically my goals are (1) the determination of the exact structures that result from the replication of DNA extremities, (2) the examination of the activities operating at the shortest telomere that triggers replicative senescence and (3) the investigation of the correspondence between telomere molecular structure and cell proliferation state at individual cell scale. To achieve this, I will undertake in Saccharomyces cerevisiae original and innovative single-molecule and single-cell approaches, that, in combination with genome-wide screens and sophisticated cellular settings, will allow to track and challenge a specified telomere of defined length. I anticipate that this work will lead to an in-depth understanding of how telomeres are replicated and how they enable the control of cell proliferation in eukaryotic cells, a matter at the intersection of the fundamentals of molecular genetics, cell biology of aging and oncology. Campo scientifico natural sciencesbiological sciencesmolecular biologymolecular geneticsnatural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencescell biologymedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticschromosomes 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-SG-LS1 - ERC Starting Grant - Molecular and Structural Biology and Biochemistry Invito a presentare proposte ERC-2010-StG_20091118 Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-SG - ERC Starting Grant Istituzione ospitante CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS Contributo UE € 1 498 503,60 Indirizzo RUE MICHEL ANGE 3 75794 Paris Francia Mostra sulla mappa Regione Ile-de-France Ile-de-France Paris Tipo di attività Research Organisations Contatto amministrativo Julie Zittel (Ms.) Ricercatore principale Maria Teresa Teixeira Fernandes Bernardo (Dr.) 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 NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS Francia Contributo UE € 1 498 503,60 Indirizzo RUE MICHEL ANGE 3 75794 Paris Mostra sulla mappa Regione Ile-de-France Ile-de-France Paris Tipo di attività Research Organisations Contatto amministrativo Julie Zittel (Ms.) Ricercatore principale Maria Teresa Teixeira Fernandes Bernardo (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato