Cel The major hallmarks of almost all cancers are aneuploidy, deregulation of the cell cycle and the reactivation of telomerase. While telomerase expression as been widely shown to ensure chromosomal stability, telomere dysfunction can be made responsible for a neuploidies universally found in cancers. Aneuploidy develops early in tumour development while telomere dysfunction is mostly found at the end of cellular life span and might induce aneuploidy directly when checkpoint functions at the end of the life span a re abrogated. This proposal addresses how the last cell cycle transitions are monitored by the cell cycle checkpoints and how loss over control of these may lead to aneuploidy.We are proposing to study the DNA damage response in normal cells that have one or more short telomeres at replicative senescence and to elucidate whether different threshold levels trigger different responses. Furthermore we propose to study the chromosomal changes in cells that have abrogated checkpoints at replicative senescence and analyse if a common tetraploidy intermediate promotes the elimination of genes that suppress cell growth and amplifies those that are associated with growth advantage, including telomerase. Our major goal is to better understand the relationship between short telomeres and the induction of genomic instability that leads to carcinogenesis. Dziedzina nauki natural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticschromosomes Program(-y) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Temat(-y) MOBILITY-2.1 - Marie Curie Intra-European Fellowships (EIF) Zaproszenie do składania wniosków FP6-2002-MOBILITY-5 Zobacz inne projekty w ramach tego zaproszenia System finansowania EIF - Marie Curie actions-Intra-European Fellowships Koordynator CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE Wkład UE Brak danych Adres Rue Michel-Ange 3 PARIS Francja Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych
