Objective
Oxidation of DNA bases by reactive oxygen species (ROS) leads to mutations that have been linked with cancer and neurodegenerations. The occurrence of these major diseases increases upon organism aging. The life expectancy in western society and particularly EU has considerably increased in the XXth century. Thus mortality caused by cancer and neurodegenerations has become massive. Therefore fighting against aging of the population is our future medical challenge and understanding mechanisms reducing the impact of oxidative DNA damages can be one of the best weapons to win this non-violent war. Mouse mutants for Nucleotide Excision Repair (NER) revealed an unexpected link between DNA damages and premature aging. The UV lesions have been for historical reason the “model lesion” for NER. However the phenotype in patients and in the several mice model of NER deficiencies together with the Oxygen Radical theory of aging suggests that endogenously generated oxidative DNA damages could be at the roots of the premature and natural aging. The molecular mechanism of NER of UV-lesions has been extensively studied but the NER of oxidative DNA lesion has not been of major focus. Our goal is to molecularly dissect the involvement of NER proteins, in the repair of oxidative DNA damages in vivo. To understand a basic process of cell physiology like mechanisms of oxidative DNA repair we will use a multidisciplinary approach with techniques spreading from mass spectrometry to live cell imaging. Our first aim would be to evaluate the recruitment of NER factors to oxidative DNA lesions generated in living cells by using confocal microscopy and a laser irradiation generating specifically those lesions. We will investigate, by mass spectrometry, for the best candidate the partners recruited during oxidative DNA repair. How DNA repair of oxidative DNA lesions occurs in a chromatin context will also be investigated by an innovative experimental design.
Fields of science
Topic(s)
Call for proposal
FP7-PEOPLE-2009-IEF
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Funding Scheme
MC-IEF - Intra-European Fellowships (IEF)Coordinator
3015 GD Rotterdam
Netherlands