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      3D visualization software to analyze topological outcomes of topoisomerase reactions

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      1 , * , 2 , 3
      Nucleic Acids Research
      Oxford University Press

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          Abstract

          The action of various DNA topoisomerases frequently results in characteristic changes in DNA topology. Important information for understanding mechanistic details of action of these topoisomerases can be provided by investigating the knot types resulting from topoisomerase action on circular DNA forming a particular knot type. Depending on the topological bias of a given topoisomerase reaction, one observes different subsets of knotted products. To establish the character of topological bias, one needs to be aware of all possible topological outcomes of intersegmental passages occurring within a given knot type. However, it is not trivial to systematically enumerate topological outcomes of strand passage from a given knot type. We present here a 3D visualization software (TopoICE-X in KnotPlot) that incorporates topological analysis methods in order to visualize, for example, knots that can be obtained from a given knot by one intersegmental passage. The software has several other options for the topological analysis of mechanisms of action of various topoisomerases.

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          Most cited references50

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          Roles of topoisomerases in maintaining steady-state DNA supercoiling in Escherichia coli.

          DNA supercoiling is essential for bacterial cell survival. We demonstrated that DNA topoisomerase IV, acting in concert with topoisomerase I and gyrase, makes an important contribution to the steady-state level of supercoiling in Escherichia coli. Following inhibition of gyrase, topoisomerase IV alone relaxed plasmid DNA to a final supercoiling density (sigma) of -0.015 at an initial rate of 0.8 links min(-1). Topoisomerase I relaxed DNA at a faster rate, 5 links min(-1), but only to a sigma of -0.05. Inhibition of topoisomerase IV in wild-type cells increased supercoiling to approximately the same level as in a mutant lacking topoisomerase I activity (to sigma = -0.08). The role of topoisomerase IV was revealed by two functional assays. Removal of both topoisomerase I and topoisomerase IV caused the DNA to become hyper-negatively supercoiled (sigma = -0.09), greatly stimulating transcription from the supercoiling sensitive leu-500 promoter and increasing the number of supercoils trapped by lambda integrase site-specific recombination.
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            Moving one DNA double helix through another by a type II DNA topoisomerase: the story of a simple molecular machine.

            Jia Wang (1998)
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              Simplification of DNA topology below equilibrium values by type II topoisomerases.

              Type II DNA topoisomerases catalyze the interconversion of DNA topoisomers by transporting one DNA segment through another. The steady-state fraction of knotted or catenated DNA molecules produced by prokaryotic and eukaryotic type II topoisomerases was found to be as much as 80 times lower than at thermodynamic equilibrium. These enzymes also yielded a tighter distribution of linking number topoisomers than at equilibrium. Thus, topoisomerases do not merely catalyze passage of randomly juxtaposed DNA segments but control a global property of DNA, its topology. The results imply that type II topoisomerases use the energy of adenosine triphosphate hydrolysis to preferentially remove the topological links that provide barriers to DNA segregation.
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                Author and article information

                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                June 2008
                24 April 2008
                24 April 2008
                : 36
                : 11
                : 3515-3521
                Affiliations
                1Department of Mathematics, University of Iowa, Iowa City, IA 52245, USA, 2Hypnagogic Software, Vancouver, BC, Canada and 3Centre for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Lausanne-Dorigny, Switzerland
                Author notes
                *To whom correspondence should be addressed. +1 319 335 0714+1 319 335 0627 idarcy@ 123456math.uiowa.edu
                Article
                gkn192
                10.1093/nar/gkn192
                2441796
                18440983
                fc7b5735-190a-4135-a10d-79a3e5d7c952
                © 2008 The Author(s)

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 January 2008
                : 31 March 2008
                : 3 April 2008
                Categories
                Computational Biology

                Genetics
                Genetics

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