The aim of the proposed project is to identify or develop compounds that are able to potentiate the DNA strand-break induced cellular poly(ADP-ribosyl)ation response. Using a flow cytometry-based poly(ADP-ribosyl)ation assay as a screening method, derivatives of L-selegiline as well as other candidate compounds described in the poly(ADP-ribosyl)ation literature shall now be tested systematically for their ability to potentiate the DNA strand-break induced cellular poly(ADP-ribosyl)ation response. The cellular effects of promising drug candidates will be further analysed with a quantitative, yet tedious biochemical assay, for validation of the data. This assay has been used by the group in the past and is currently being developed further, using mass spectrometry as a readout. The next step is the identification of the underlying molecular mechanisms. This shall be done by using biochemical methods as well as genetically modified cell cultures. One important end point to study will the formation and repair of DNA strand breaks in living cells challenged with genotoxic agents, using the automated FADU assay.
