New mechanistic and functional insights into DNA topoisomerases

DNA topoisomerases are nature's tools for resolving the unique problems of DNA entanglement that occur owing to unwinding and rewinding of the DNA helix during replication, transcription, recombination, repair, and chromatin remodeling. These enzymes perform topological transformations by provi...

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Bibliographic Details
Published in:Annual review of biochemistry 2013-01, Vol.82 (1), p.139-170
Main Authors: Chen, Stefanie Hartman, Chan, Nei-Li, Hsieh, Tao-shih
Format: Article
Language:English
Subjects:
Antibiotics
Antineoplastic Agents - pharmacology
Biochemistry
Catalytic Domain
Chromatin
Cytotoxicity
Deoxyribonucleic acid
DNA
DNA - genetics
DNA - metabolism
DNA Replication
DNA Topoisomerases, Type I - chemistry
DNA Topoisomerases, Type I - genetics
DNA Topoisomerases, Type I - metabolism
DNA Topoisomerases, Type II - chemistry
DNA Topoisomerases, Type II - genetics
DNA Topoisomerases, Type II - metabolism
Enzymes
Humans
Pharmaceuticals
Protein Structure, Tertiary
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Summary:DNA topoisomerases are nature's tools for resolving the unique problems of DNA entanglement that occur owing to unwinding and rewinding of the DNA helix during replication, transcription, recombination, repair, and chromatin remodeling. These enzymes perform topological transformations by providing a transient DNA break, formed by a covalent adduct with the enzyme, through which strand passage can occur. The active site tyrosine is responsible for initiating two transesterifications to cleave and then religate the DNA backbone. The cleavage reaction intermediate is exploited by cytotoxic agents, which have important applications as antibiotics and anticancer drugs. The reactions mediated by these enzymes can also be regulated by their binding partners; one example is a DNA helicase capable of modulating the directionality of strand passage, enabling important functions like reannealing denatured DNA and resolving recombination intermediates. In this review, we cover recent advances in mechanistic insights into topoisomerases and their various cellular functions.
ISSN:0066-4154
1545-4509
DOI:10.1146/annurev-biochem-061809-100002