Topoisomerase Inhibitors

Topoisomerases temporarily break DNA strands and perform topological changes to selected regions of the genome available for transcription. Two main classes of topoisomerases are recognized to date: topoisomerases I and II. Topoisomerase I catalyzes the ATP-independent relaxation of DNA supercoils by transiently breaking and religating single-stranded DNA. Topoisomerase II relaxes supercoiled DNA through catalysis of a transient breakage of double-stranded DNA in an ATP-dependent manner. Examples of topoisomerase inhibitors are etoposide and camptothecin, which form a stable ternary DNA-topoisomerase II drug complex that maintains a cleaved state of DNA and interferes with DNA replication, repair, and transcription of eukaryotic cells (Fig. 80).

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