Abstract
It is now known that several antimicrobial and antitumor drugs destroy cells by interacting with cellular DNA topoisomerases. These enzymes are ubiquitous in nature and are required for the regulation of DNA structure (topology) in the cell. Specifically, DNA topoisomerases regulate the coiling of the DNA double helix, a parameter critical for processes such as replication and transcription. Topoisomerases alter DNA coiling by transiently cleaving DNA. They have been defined mechanistically as type I if they nick a single strand of the DNA double helix and type II if they cleave both strands. The discovery of antitumor drugs that specifically target topoisomerases has not only led to an improved understanding of tumor cell biology but has also fostered the rapid development of new anticancer drugs. This chapter reviews the anticancer drugs that target topoisomerases and focuses on cellular mechanisms of resistance to these drugs.
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