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Chromatinization modulates topoisomerase II processivity

Type IIA topoisomerases are essential DNA processing enzymes that must robustly and reliably relax DNA torsional stress. While cellular processes constantly create varying torsional stress, how this variation impacts type IIA topoisomerase function remains obscure. Using multiple single-molecule app...

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Autores principales: Lee, Jaeyoon, Wu, Meiling, Inman, James T., Singh, Gundeep, Park, Seong ha, Lee, Joyce H., Fulbright, Robert M., Hong, Yifeng, Jeong, Joshua, Berger, James M., Wang, Michelle D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10611788/
https://www.ncbi.nlm.nih.gov/pubmed/37891161
http://dx.doi.org/10.1038/s41467-023-42600-z
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author Lee, Jaeyoon
Wu, Meiling
Inman, James T.
Singh, Gundeep
Park, Seong ha
Lee, Joyce H.
Fulbright, Robert M.
Hong, Yifeng
Jeong, Joshua
Berger, James M.
Wang, Michelle D.
author_facet Lee, Jaeyoon
Wu, Meiling
Inman, James T.
Singh, Gundeep
Park, Seong ha
Lee, Joyce H.
Fulbright, Robert M.
Hong, Yifeng
Jeong, Joshua
Berger, James M.
Wang, Michelle D.
author_sort Lee, Jaeyoon
collection PubMed
description Type IIA topoisomerases are essential DNA processing enzymes that must robustly and reliably relax DNA torsional stress. While cellular processes constantly create varying torsional stress, how this variation impacts type IIA topoisomerase function remains obscure. Using multiple single-molecule approaches, we examined the torsional dependence of eukaryotic topoisomerase II (topo II) activity on naked DNA and chromatin. We observed that topo II is ~50-fold more processive on buckled DNA than previously estimated. We further discovered that topo II relaxes supercoiled DNA prior to plectoneme formation, but with processivity reduced by ~100-fold. This relaxation decreases with diminishing torsion, consistent with topo II capturing transient DNA loops. Topo II retains high processivity on buckled chromatin (~10,000 turns) and becomes highly processive even on chromatin under low torsional stress (~1000 turns), consistent with chromatin’s predisposition to readily form DNA crossings. This work establishes that chromatin is a major stimulant of topo II function.
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spelling pubmed-106117882023-10-29 Chromatinization modulates topoisomerase II processivity Lee, Jaeyoon Wu, Meiling Inman, James T. Singh, Gundeep Park, Seong ha Lee, Joyce H. Fulbright, Robert M. Hong, Yifeng Jeong, Joshua Berger, James M. Wang, Michelle D. Nat Commun Article Type IIA topoisomerases are essential DNA processing enzymes that must robustly and reliably relax DNA torsional stress. While cellular processes constantly create varying torsional stress, how this variation impacts type IIA topoisomerase function remains obscure. Using multiple single-molecule approaches, we examined the torsional dependence of eukaryotic topoisomerase II (topo II) activity on naked DNA and chromatin. We observed that topo II is ~50-fold more processive on buckled DNA than previously estimated. We further discovered that topo II relaxes supercoiled DNA prior to plectoneme formation, but with processivity reduced by ~100-fold. This relaxation decreases with diminishing torsion, consistent with topo II capturing transient DNA loops. Topo II retains high processivity on buckled chromatin (~10,000 turns) and becomes highly processive even on chromatin under low torsional stress (~1000 turns), consistent with chromatin’s predisposition to readily form DNA crossings. This work establishes that chromatin is a major stimulant of topo II function. Nature Publishing Group UK 2023-10-27 /pmc/articles/PMC10611788/ /pubmed/37891161 http://dx.doi.org/10.1038/s41467-023-42600-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Lee, Jaeyoon
Wu, Meiling
Inman, James T.
Singh, Gundeep
Park, Seong ha
Lee, Joyce H.
Fulbright, Robert M.
Hong, Yifeng
Jeong, Joshua
Berger, James M.
Wang, Michelle D.
Chromatinization modulates topoisomerase II processivity
title Chromatinization modulates topoisomerase II processivity
title_full Chromatinization modulates topoisomerase II processivity
title_fullStr Chromatinization modulates topoisomerase II processivity
title_full_unstemmed Chromatinization modulates topoisomerase II processivity
title_short Chromatinization modulates topoisomerase II processivity
title_sort chromatinization modulates topoisomerase ii processivity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10611788/
https://www.ncbi.nlm.nih.gov/pubmed/37891161
http://dx.doi.org/10.1038/s41467-023-42600-z
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