DNA Topoisomerases

Topoisomerases are ubiquitously expressed enzymes that overcome topological problems in genomic DNA, which can result from DNA replication, transcription and repair. Common problems such as overwinding (positive supercoiling), knots and tangles are resolved by topoisomerases by catalyzing the breaking of one or two strands of DNA.

Topoisomerase type I enzymes cut just one strand of the DNA double helix, and therefore relax supercoiling of the DNA. Four genes encode Type I topoisomerases, which include nuclear topoisomerase I (TOP1) and mitochondrial topoisomerase I (TOP1MT). Type I enzymes can also be sub-divided into Types A and B based on their different catalytic mechanism for generating single DNA strand breaks. TOP1 and TOP1MT are both type 1B since they form 3'-phosphotyrosyl bonds. Camptothecin is a natural product inhibitor of TOP1 that has led to the discovery of derivatives that are clinically used anticancer drugs. Such inhibitors trap the enzyme in a cleavage complex with DNA. Type II topoisomerases (IIA and IIB) are particular important for the disentanglement of DNA, which is overcome by generating double stranded DNA breaks. Dysregulation of type II enzymes can therefore have a potentially significant genotoxic effect. There is a broad range of topoisomerase II inhibitors that are used clinically as therapeutically in cancer.

External sources of pharmacological information for DNA Topoisomerases :

• BJP Guide

Literature for DNA Topoisomerases

Tocris offers the following scientific literature for DNA Topoisomerases to showcase our products. We invite you to request* your copy today!

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Huntington's Disease Research Product Guide

This product guide provides a background to Huntington's disease research and lists around 100 products for the study of:

• Somatic Instability
• Proteolysis and Inclusion Bodies
• Transcriptional Dysregulation
• Mitochondrial Dysfunction
• Nuclear-Cytoplasmic Transport Interference
• Excitotoxicity
• Stem Cells

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Cell Cycle & DNA Damage Repair Poster

In normal cells, each stage of the cell cycle is tightly regulated, however in cancer cells many genes and proteins that are involved in the regulation of the cell cycle are mutated or over expressed. This poster summarizes the stages of the cell cycle and DNA repair. It also highlights strategies for enhancing replicative stress in cancer cells to force mitotic catastrophe and cell death.

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Topoisomerase Gene Data