0DNA topoisomerase I (Top1) regulate DNA supercoiling both in the nucleus and mitochondria to enable reliable transmission of our genetic information to the offspring. However, Top1 are toxic when trapped on the DNA (Top1-cleavage complexes; Top1cc) in the presence of anticancer drug camptothecin (CPT), a naturally occurring quinoline alkaloid. Despite the chemical success of Top1 inhibitors like CPT and its derivatives in cancer chemotherapy, inherent resistance has been reported with significant limitations. The cellular role of human tyrosyl DNA phosphodiesterase 1 (TDP1), a key enzyme responsible for the repair of Top1-induced DNA damage and identify TDP1 as a co-target for combinatorial anticancer drug therapy along with Top1 poisons.
