Topoisomerase II has been identified as the primary cellular target for a number of antitumor drugs currently being used in cancer chemotherapy. Topoisomerase I has also been found to be the target of camptothecin, an antitumor drug currently under development. Topoisomerases normally solve the topological problems of DN A, which are generated during replication, transcription and recombination, by breaking and rejoining the DNA strands. Topoisomerase-active antitumor drugs interfere with the breakage and rejoining reaction of topoisomerases by trapping an abortive enzyme-DNA “cleavable complex”. The formation of drug-induced “cleavable complexes” effectively converts the enzyme into a cellular poison. The high cellular level of topoisomerase II in some tumors may partly explain the high therapeutic index of these antitumor drugs. Studies of this type of DNA lesion are likely to provide important new information concerning the mechanism of cell killing by antitumor drugs.
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Bodley, A., Liu, L. Topoisomerases as Novel Targets for Cancer Chemotherapy. Nat Biotechnol 6, 1315–1319 (1988). https://doi.org/10.1038/nbt1188-1315
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