Nucleic Acids Research Advance Access originally published online on July 25, 2008
Nucleic Acids Research 2008 36(15):4956-4963; doi:10.1093/nar/gkn467
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Nucleic Acids Research, 2008, Vol. 36, No. 15 4956-4963
© 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.
Computational Biology |
DNA supercoiling inhibits DNA knotting
Center for Integrative Genomics, University of Lausanne, CH-1015 Lausanne, Switzerland
*To whom correspondence should be addressed. Tel: +41 21 692 4282; Fax: +41 21 692 4105; Email: andrzej.stasiak{at}unil.ch
Received May 23, 2008. Revised July 2, 2008. Accepted July 3, 2008.
Despite the fact that in living cells DNA molecules are long and highly crowded, they are rarely knotted. DNA knotting interferes with the normal functioning of the DNA and, therefore, molecular mechanisms evolved that maintain the knotting and catenation level below that which would be achieved if the DNA segments could pass randomly through each other. Biochemical experiments with torsionally relaxed DNA demonstrated earlier that type II DNA topoisomerases that permit inter- and intramolecular passages between segments of DNA molecules use the energy of ATP hydrolysis to select passages that lead to unknotting rather than to the formation of knots. Using numerical simulations, we identify here another mechanism by which topoisomerases can keep the knotting level low. We observe that DNA supercoiling, such as found in bacterial cells, creates a situation where intramolecular passages leading to knotting are opposed by the free-energy change connected to transitions from unknotted to knotted circular DNA molecules.
Present address: Yannis Burnier, Department of Physics, University of Bielefeld, D-33615 Bielefeld, Germany
Julien Dorieer, Institute of Theoretical Physics, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors
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