Topoisomerase inhibitors

Topoisomerase enzymes are a family of nuclear proteins with essential functions in regulating the topology of the DNA helix. Topoisomerase proteins appear to constantly monitor DNA structure, looking for points of increased tension. The protein then alters DNA tertiary structure, by creating transient strand breakage in DNA backbone. Eukaryotics has two forms of topoisomerase enzyme:

♦ Topoisomerase I (topoI) binds to double-stranded DNA and cleaves and religates one strand of duplex DNA. Relaxation of supercoiled DNA is then used during processes of replication, transcription, and recombination.

♦ Topoisomerase II (topoII) creates transient double-stranded breakage of DNA, allowing subsequent passage of a second intact DNA duplex through the break.

Biochemical analysis has identified camptothecin (CPT) and its analogues as inhibitors of topoI, while epipodophyllotoxins, etoposide and teniposide, are inhibitors of topoII.

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