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Two convergent pathways of DNA knotting in replicating DNA molecules as revealed by θ-curve analysis
During DNA replication in living cells some DNA knots are inadvertently produced by DNA topoisomerases facilitating progression of replication forks. The types of DNA knots formed are conditioned by the 3D organization of replicating DNA molecules. Therefore, by characterizing formed DNA knots it is...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158496/ https://www.ncbi.nlm.nih.gov/pubmed/29982678 http://dx.doi.org/10.1093/nar/gky559 |
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author | O’Donnol, Danielle Stasiak, Andrzej Buck, Dorothy |
author_facet | O’Donnol, Danielle Stasiak, Andrzej Buck, Dorothy |
author_sort | O’Donnol, Danielle |
collection | PubMed |
description | During DNA replication in living cells some DNA knots are inadvertently produced by DNA topoisomerases facilitating progression of replication forks. The types of DNA knots formed are conditioned by the 3D organization of replicating DNA molecules. Therefore, by characterizing formed DNA knots it is possible to infer the 3D arrangement of replicating DNA molecules. This topological inference method is highly developed for knotted DNA circles. However, partially replicated DNA molecules have the form of θ-curves. In this article, we use mathematical formalism of θ-curves to characterize the full possibilities of how knotting can occur during replication of DNA molecules in vivo. To do this, we reanalyze earlier experimental studies of knotted, partially replicated DNA molecules and the previously proposed pathway of their formation. We propose a general model of knotting in replication intermediates, and demonstrate that there is an additional, equally important, parallel knotting pathway that also explains how DNA topoisomerases can produce experimentally observed knotted θ-curves. Interestingly, both pathways require intertwining of freshly replicated sister duplexes (precatenanes). |
format | Online Article Text |
id | pubmed-6158496 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-61584962018-10-02 Two convergent pathways of DNA knotting in replicating DNA molecules as revealed by θ-curve analysis O’Donnol, Danielle Stasiak, Andrzej Buck, Dorothy Nucleic Acids Res Structural Biology During DNA replication in living cells some DNA knots are inadvertently produced by DNA topoisomerases facilitating progression of replication forks. The types of DNA knots formed are conditioned by the 3D organization of replicating DNA molecules. Therefore, by characterizing formed DNA knots it is possible to infer the 3D arrangement of replicating DNA molecules. This topological inference method is highly developed for knotted DNA circles. However, partially replicated DNA molecules have the form of θ-curves. In this article, we use mathematical formalism of θ-curves to characterize the full possibilities of how knotting can occur during replication of DNA molecules in vivo. To do this, we reanalyze earlier experimental studies of knotted, partially replicated DNA molecules and the previously proposed pathway of their formation. We propose a general model of knotting in replication intermediates, and demonstrate that there is an additional, equally important, parallel knotting pathway that also explains how DNA topoisomerases can produce experimentally observed knotted θ-curves. Interestingly, both pathways require intertwining of freshly replicated sister duplexes (precatenanes). Oxford University Press 2018-09-28 2018-06-30 /pmc/articles/PMC6158496/ /pubmed/29982678 http://dx.doi.org/10.1093/nar/gky559 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Structural Biology O’Donnol, Danielle Stasiak, Andrzej Buck, Dorothy Two convergent pathways of DNA knotting in replicating DNA molecules as revealed by θ-curve analysis |
title | Two convergent pathways of DNA knotting in replicating DNA molecules as revealed by θ-curve analysis |
title_full | Two convergent pathways of DNA knotting in replicating DNA molecules as revealed by θ-curve analysis |
title_fullStr | Two convergent pathways of DNA knotting in replicating DNA molecules as revealed by θ-curve analysis |
title_full_unstemmed | Two convergent pathways of DNA knotting in replicating DNA molecules as revealed by θ-curve analysis |
title_short | Two convergent pathways of DNA knotting in replicating DNA molecules as revealed by θ-curve analysis |
title_sort | two convergent pathways of dna knotting in replicating dna molecules as revealed by θ-curve analysis |
topic | Structural Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158496/ https://www.ncbi.nlm.nih.gov/pubmed/29982678 http://dx.doi.org/10.1093/nar/gky559 |
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