Objective
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciencesbiological sciencesgeneticsDNA
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesclinical medicineoncology
- natural sciencesbiological sciencesgeneticschromosomes
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Call for proposal
FP6-2002-MOBILITY-5
See other projects for this call
Funding Scheme
EIF - Marie Curie actions-Intra-European FellowshipsCoordinator
PARIS
France