DNA Topoisomerases

Supporting information

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.

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Gene Species Gene Symbol Gene Accession No. Protein Accession No.
Topoisomerase I Human TOP1 NM_003286 P11387
Mouse Top1 NM_009408 Q04750
Rat Top1 NM_022615 Q9WUL0
Topoisomerase I (mitochondrial) Human TOP1MT NM_052963 Q969P6
Mouse Top1mt NM_028404 NP_082680
Rat Top1mt NM_001002798 Q6IM78
View all Topoisomerase Gene Data »

Literature for DNA Topoisomerases

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