Topoisomerases

Abstract

Topoisomerases are enzymes that interconvert different topological states of DNA, such as levels of supercoiling, catenanes (links) and knots. They are vital to all DNA‐related processes and are the targets for a number of antibacterial and anticancer agents.

Keywords: DNA topology; gyrase; replication; anticancer agents; antibacterials

Figure 1.

The reactions carried out by topoisomerases. (a) Supercoiling/relaxation. (b) Catenation/decatenation. (c) Knotting/unknotting. Double‐stranded DNA is represented as a solid tube.

Figure 2.

Three‐dimensional structures of topoisomerase fragments. The three‐dimensional structures are represented as ribbons following the protein main chains. The active‐site tyrosine residues (see text) are shown as yellow spheres, and monomer subunits of dimeric structures are coloured red and blue. (a) 67‐kDa Escherichia coli topoisomerase I fragment. The domains are coloured arbitrarily to emphasize the two halves of the molecule. (b) 43 kDa N‐terminal ATPase fragment of E. coli GyrB. The 5′‐adenylyl‐β,γ‐imidodiphosphate (ADPNP) molecules are indicated in yellow. (c) 92‐kDa fragment of Saccharomyces cerevisiae topoisomerase II. (d) 59‐kDa N‐terminal fragment of E. coli GyrA. The figures were generated using RasMol 2.6 from crystallographic coordinates described in Lima et al., Wigley et al., Berger et al. and Morais Cabral et al.. The coordinates were acquired from the Protein Data Bank (Abola et al., ) apart from (b) which was acquired from DB Wigley (personal communication).

Figure 4.

Alignment of the protein sequences of type II topoisomerases. Saccharomyces cerevisiae topoisomerase II and the two subunits of Escherichia coliDNA gyrase are aligned. The purple regions show no sequence similarity. The ‘insert’ region is present in a subset of GyrB sequences, but in no topoisomerase IIs. The active‐site tyrosine residues are indicated by a Y, and the regions corresponding to the structures in Figure are indicated as black bars.

Figure 3.

Mechanistic models of topoisomerases. (a) Type IA topoisomerases. (b) Type IB topoisomerases (based on Stewart et al.. (c) Type II topoisomerases. Separate domains or monomers are shown in red and blue, active‐site tyrosines in yellow, and ATP as yellow ellipses. See text for mechanistic details.

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References

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Lima CD, Wang JC and Mondragón A (1994) Three‐dimensional structure of the 67K N‐terminal fragment of E. coli DNA topoisomerase I. Nature 367: 138–146.

Liu LF and Wang JC (1987) Supercoiling of the DNA template during transcription. Proceedings of the National Academy of Sciences of the USA 84: 7024–7027.

Morais Cabral JH, Jackson AP, Smith CV et al. (1997) Crystal structure of the breakage‐reunion domain of DNA gyrase. Nature 388: 903–906.

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Further Reading

Bates AD and Maxwell A (1993) DNA Topology. Oxford: IRL Press.

Berger JM (1998) Type II DNA topoisomerases. Current Opinion in Structural Biology 8: 26–32.

Champoux JJ (1998) Domains of human topoisomerase I and associated functions. Progress in Nucleic Acid Research and Molecular Biology 60: 111–132.

Chen AY and Liu LF (1994) DNA topoisomerases: essential enzymes and lethal targets. Annual Review of Pharmacology and Toxicology 34: 191–218.

Duguet M (1997) When helicase and topoisomerase meet! Journal of Cell Science 110: 1345–1350.

Maxwell A (1997) DNA gyrase as a drug target. Trends in Microbiology 5: 102–109.

Sharma A and Mondragón A (1995) DNA topoisomerases. Current Opinion in Structural Biology 5: 39–47.

Wang JC (1991) DNA topoisomerases: why so many? Journal of Biological Chemistry 266: 6659–6662.

Wang JC (1996) DNA topoisomerases. Annual Review of Biochemistry 65: 635–692.

Wang JC (1998) Moving one DNA double helix through another by a type II DNA topoisomerase: the story of a simple molecular machine. Quarterly Reviews in Biophysics 31: 107–144.

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How to Cite close
Bates, Andrew D(Apr 2001) Topoisomerases. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0001039]