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DNA knots occur in intracellular chromatin

In vivo DNA molecules are narrowly folded within chromatin fibers and self-interacting chromatin domains. Therefore, intra-molecular DNA entanglements (knots) might occur via DNA strand passage activity of topoisomerase II. Here, we assessed the presence of such DNA knots in a variety of yeast circu...

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Autores principales: Valdés, Antonio, Segura, Joana, Dyson, Sílvia, Martínez-García, Belén, Roca, Joaquim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778459/
https://www.ncbi.nlm.nih.gov/pubmed/29149297
http://dx.doi.org/10.1093/nar/gkx1137
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author Valdés, Antonio
Segura, Joana
Dyson, Sílvia
Martínez-García, Belén
Roca, Joaquim
author_facet Valdés, Antonio
Segura, Joana
Dyson, Sílvia
Martínez-García, Belén
Roca, Joaquim
author_sort Valdés, Antonio
collection PubMed
description In vivo DNA molecules are narrowly folded within chromatin fibers and self-interacting chromatin domains. Therefore, intra-molecular DNA entanglements (knots) might occur via DNA strand passage activity of topoisomerase II. Here, we assessed the presence of such DNA knots in a variety of yeast circular minichromosomes. We found that small steady state fractions of DNA knots are common in intracellular chromatin. These knots occur irrespective of DNA replication and cell proliferation, though their abundance is reduced during DNA transcription. We found also that in vivo DNA knotting probability does not scale proportionately with chromatin length: it reaches a value of ∼0.025 in domains of ∼20 nucleosomes but tends to level off in longer chromatin fibers. These figures suggest that, while high flexibility of nucleosomal fibers and clustering of nearby nucleosomes facilitate DNA knotting locally, some mechanism minimizes the scaling of DNA knot formation throughout intracellular chromatin. We postulate that regulation of topoisomerase II activity and the fractal architecture of chromatin might be crucial to prevent a potentially massive and harmful self-entanglement of DNA molecules in vivo.
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spelling pubmed-57784592018-01-30 DNA knots occur in intracellular chromatin Valdés, Antonio Segura, Joana Dyson, Sílvia Martínez-García, Belén Roca, Joaquim Nucleic Acids Res Gene regulation, Chromatin and Epigenetics In vivo DNA molecules are narrowly folded within chromatin fibers and self-interacting chromatin domains. Therefore, intra-molecular DNA entanglements (knots) might occur via DNA strand passage activity of topoisomerase II. Here, we assessed the presence of such DNA knots in a variety of yeast circular minichromosomes. We found that small steady state fractions of DNA knots are common in intracellular chromatin. These knots occur irrespective of DNA replication and cell proliferation, though their abundance is reduced during DNA transcription. We found also that in vivo DNA knotting probability does not scale proportionately with chromatin length: it reaches a value of ∼0.025 in domains of ∼20 nucleosomes but tends to level off in longer chromatin fibers. These figures suggest that, while high flexibility of nucleosomal fibers and clustering of nearby nucleosomes facilitate DNA knotting locally, some mechanism minimizes the scaling of DNA knot formation throughout intracellular chromatin. We postulate that regulation of topoisomerase II activity and the fractal architecture of chromatin might be crucial to prevent a potentially massive and harmful self-entanglement of DNA molecules in vivo. Oxford University Press 2018-01-25 2017-11-15 /pmc/articles/PMC5778459/ /pubmed/29149297 http://dx.doi.org/10.1093/nar/gkx1137 Text en © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Gene regulation, Chromatin and Epigenetics
Valdés, Antonio
Segura, Joana
Dyson, Sílvia
Martínez-García, Belén
Roca, Joaquim
DNA knots occur in intracellular chromatin
title DNA knots occur in intracellular chromatin
title_full DNA knots occur in intracellular chromatin
title_fullStr DNA knots occur in intracellular chromatin
title_full_unstemmed DNA knots occur in intracellular chromatin
title_short DNA knots occur in intracellular chromatin
title_sort dna knots occur in intracellular chromatin
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778459/
https://www.ncbi.nlm.nih.gov/pubmed/29149297
http://dx.doi.org/10.1093/nar/gkx1137
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