Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |
_version_ | 1785128560583770112 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10611788 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT leejaeyoon chromatinizationmodulatestopoisomeraseiiprocessivity AT wumeiling chromatinizationmodulatestopoisomeraseiiprocessivity AT inmanjamest chromatinizationmodulatestopoisomeraseiiprocessivity AT singhgundeep chromatinizationmodulatestopoisomeraseiiprocessivity AT parkseongha chromatinizationmodulatestopoisomeraseiiprocessivity AT leejoyceh chromatinizationmodulatestopoisomeraseiiprocessivity AT fulbrightrobertm chromatinizationmodulatestopoisomeraseiiprocessivity AT hongyifeng chromatinizationmodulatestopoisomeraseiiprocessivity AT jeongjoshua chromatinizationmodulatestopoisomeraseiiprocessivity AT bergerjamesm chromatinizationmodulatestopoisomeraseiiprocessivity AT wangmichelled chromatinizationmodulatestopoisomeraseiiprocessivity |