Objective
Structure-specific endonucleases are key players in the maintenance of genome integrity. They act as specialized surgical tools for the processing of secondary DNA structures generated during important DNA repair and recombination events. However, cleaving DNA opens windows of opportunity for the occurrence of potentially dangerous chromosome rearrangements at the origin of cancer.
The action of structure-specific endonucleases must therefore be tightly coordinated with downstream events that restore the full integrity of the chromosome. Additional challenge for the cell stems from the fact that for many of these nucleases the minimal structural requirement for cleaving DNA is a junction between double-strand and single-strand DNA.
Therefore, in addition to controlling these enzymes in the context of their physiological reaction, the cell must ensure that they do not act randomly on structures generated during other DNA transactions associated with DNA unwinding. Despite their fundamental nature, the mechanisms that control structure-specific endonucleases remain poorly understood.
This research project proposes to tackle this fundamental question by focusing on a conserved class of eukaryote heteromeric structure-specific endonucleases, each involved in sever al DNA repair and recombination pathways. A detailed analysis of the regulation of these endonucleases will be carried out throughout the cell-cycle and in response to genotoxic stresses in the fission yeast Schizosaccharomyces pombe; a proven model system for the analysis and understanding of evolutionary conserved processes involved in genome maintenance in higher eukaryotes.
The remarkable investigational potential of S. pombe will allow to combine genetic and cellular analysis with proteomic and biochemical studies. Results from our investigations in yeast will provide a platform to extend our analyses to mammalian cells, with a constant focus on assessing their relevance in the context of cancer biology.
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
- medical and health sciencesclinical medicineoncology
- natural sciencesbiological sciencesgeneticschromosomes
- natural sciencesbiological sciencesgeneticsgenomes
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
Call for proposal
FP6-2004-MOBILITY-12
See other projects for this call
Funding Scheme
EIF - Marie Curie actions-Intra-European FellowshipsCoordinator
PARIS
France