High-content screen for DNA repair inhibitors

We have recently developed the first whole-cell, high-content assay for the discovery of inhibitors of non-homologous end joining and homologous recombination repair, the primary pathways by which DNA double-strand breaks are ameliorated.  This assay is based on the concurrent analysis of γH2AX and 53BP1 foci, which are two essential factors involved in the DNA damage response.  Using this assay, we discovered that certain cardiac glycoside natural products are potent inhibitors of DNA repair.  We are currently planning to apply this assay to hundreds of thousands of compounds to identify novel molecular scaffolds for development.  Congratulations to our good friend Yulia Surovtseva and to our collaborators in the Bindra lab!