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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...

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Autores principales: O’Donnol, Danielle, Stasiak, Andrzej, Buck, Dorothy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
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).
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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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