Objective Medal and 53BP1 have recently emerged as the key components of the cellular defence machinery, which guards against adverse effects of geotaxis stress. This research proposal embarks on elucidating of how phosphorylation of Medal and 53BP1 regulates genetic stability in human cells.Task 1 aim at mapping of phosphorylation sites of Medal and 53BP1 induced by DNA damage and/or replication stress.Task 2 includes generation of the phosphor-deficient and mimicking-mimicking mutants of Mac and 53BP1 and establishing human cell lines enabling to conditionally express these mutants after down regulation of the endogenous wild-type counterparts by RNA interference. Task 3 focuses on a comprehensive analysis of the roles of the 53BP1 and Medal phosphorylation for the kinetics and velocity of the DNA damage response using a battery of state-of-art molecular, biochemical and cell biology approaches including imaging of the key underlying biochemical reactions in live cells.Task 4 aims at generation of specific-specific antibodies to the identified residues-residues of Medal and 53BP1. Among others, these reagents will be employed in a broad immune- photochemical survey to study the potential cancer-associated checkpoint defects. The proposed experiments are expected to significantly broaden our knowledge about the fundamental genome safeguarding mechanisms and provide tools to identify how these mechanisms are subverted in human disease. Fields of science natural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencescell biologynatural sciencesbiological sciencesgeneticsRNAnatural sciencesbiological sciencesgeneticsgenomes Keywords Cancer DNA repair cell cycle Programme(s) 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 Topic(s) MOBILITY-2.1 - Marie Curie Intra-European Fellowships (EIF) Call for proposal FP6-2002-MOBILITY-5 See other projects for this call Funding Scheme EIF - Marie Curie actions-Intra-European Fellowships Coordinator DANISH CANCER SOCIETY EU contribution No data Address Strandboulevarden 49 COPENHAGE Denmark See on map Total cost No data
