The objectives of this proposal are to develop gene silencing reagents, and to test/validate their use in synthetic lethal screening of DNA damage signaling and repair pathways. Making such reagents available will provide the efficiency and convenience that cancer researchers currently need to find novel strategies and therapeutics against cancer. DNA repair pathway genes have been shown to encode important factors in cancer biogenesis. Targeting different networks within this pathway may be a promising point of action for curing cancer. The proposed research can facilitate the efforts in finding such cures. The research plan includes a novel combination of a number of essential elements, for example, highly efficient construction of lentiviruses carrying shRNA and use of surrogate targets for gene silencing assays.