DNA damage response (DDR) network is essential for prevention of accumulation of harmful mutations leading to various diseases and tumourigenesis. DDR functions as a cooperation of parallel alternative pathways, buffering each other. Partial disturbance of DDR network in cancer cells make them critically dependent on a single repairing pathway. Such genetic changes in tumour cells predispose them for the therapy by targeting DDR mechanism. This redundancy can be exploited with synthetic lethality (SL) approach. The goal of this proposal is to validate FEN1-MRE11 SL partnership in cancer cells and chemically target it with novel inhibitors of Mre11.The results of this proposal should provide a novel strategy to treat DNA repair-defective tumours with minimal side-effects for the organism.