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Fission yeast condensin contributes to interphase chromatin organization and prevents transcription-coupled DNA damage

BACKGROUND: Structural maintenance of chromosomes (SMC) complexes are central organizers of chromatin architecture throughout the cell cycle. The SMC family member condensin is best known for establishing long-range chromatin interactions in mitosis. These compact chromatin and create mechanically s...

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Autores principales: Kakui, Yasutaka, Barrington, Christopher, Barry, David J., Gerguri, Tereza, Fu, Xiao, Bates, Paul A., Khatri, Bhavin S., Uhlmann, Frank
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643427/
https://www.ncbi.nlm.nih.gov/pubmed/33153481
http://dx.doi.org/10.1186/s13059-020-02183-0
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author Kakui, Yasutaka
Barrington, Christopher
Barry, David J.
Gerguri, Tereza
Fu, Xiao
Bates, Paul A.
Khatri, Bhavin S.
Uhlmann, Frank
author_facet Kakui, Yasutaka
Barrington, Christopher
Barry, David J.
Gerguri, Tereza
Fu, Xiao
Bates, Paul A.
Khatri, Bhavin S.
Uhlmann, Frank
author_sort Kakui, Yasutaka
collection PubMed
description BACKGROUND: Structural maintenance of chromosomes (SMC) complexes are central organizers of chromatin architecture throughout the cell cycle. The SMC family member condensin is best known for establishing long-range chromatin interactions in mitosis. These compact chromatin and create mechanically stable chromosomes. How condensin contributes to chromatin organization in interphase is less well understood. RESULTS: Here, we use efficient conditional depletion of fission yeast condensin to determine its contribution to interphase chromatin organization. We deplete condensin in G2-arrested cells to preempt confounding effects from cell cycle progression without condensin. Genome-wide chromatin interaction mapping, using Hi-C, reveals condensin-mediated chromatin interactions in interphase that are qualitatively similar to those observed in mitosis, but quantitatively far less prevalent. Despite their low abundance, chromatin mobility tracking shows that condensin markedly confines interphase chromatin movements. Without condensin, chromatin behaves as an unconstrained Rouse polymer with excluded volume, while condensin constrains its mobility. Unexpectedly, we find that condensin is required during interphase to prevent ongoing transcription from eliciting a DNA damage response. CONCLUSIONS: In addition to establishing mitotic chromosome architecture, condensin-mediated long-range chromatin interactions contribute to shaping chromatin organization in interphase. The resulting structure confines chromatin mobility and protects the genome from transcription-induced DNA damage. This adds to the important roles of condensin in maintaining chromosome stability.
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spelling pubmed-76434272020-11-06 Fission yeast condensin contributes to interphase chromatin organization and prevents transcription-coupled DNA damage Kakui, Yasutaka Barrington, Christopher Barry, David J. Gerguri, Tereza Fu, Xiao Bates, Paul A. Khatri, Bhavin S. Uhlmann, Frank Genome Biol Research BACKGROUND: Structural maintenance of chromosomes (SMC) complexes are central organizers of chromatin architecture throughout the cell cycle. The SMC family member condensin is best known for establishing long-range chromatin interactions in mitosis. These compact chromatin and create mechanically stable chromosomes. How condensin contributes to chromatin organization in interphase is less well understood. RESULTS: Here, we use efficient conditional depletion of fission yeast condensin to determine its contribution to interphase chromatin organization. We deplete condensin in G2-arrested cells to preempt confounding effects from cell cycle progression without condensin. Genome-wide chromatin interaction mapping, using Hi-C, reveals condensin-mediated chromatin interactions in interphase that are qualitatively similar to those observed in mitosis, but quantitatively far less prevalent. Despite their low abundance, chromatin mobility tracking shows that condensin markedly confines interphase chromatin movements. Without condensin, chromatin behaves as an unconstrained Rouse polymer with excluded volume, while condensin constrains its mobility. Unexpectedly, we find that condensin is required during interphase to prevent ongoing transcription from eliciting a DNA damage response. CONCLUSIONS: In addition to establishing mitotic chromosome architecture, condensin-mediated long-range chromatin interactions contribute to shaping chromatin organization in interphase. The resulting structure confines chromatin mobility and protects the genome from transcription-induced DNA damage. This adds to the important roles of condensin in maintaining chromosome stability. BioMed Central 2020-11-05 /pmc/articles/PMC7643427/ /pubmed/33153481 http://dx.doi.org/10.1186/s13059-020-02183-0 Text en © The Author(s) 2020 Open AccessThis 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/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Kakui, Yasutaka
Barrington, Christopher
Barry, David J.
Gerguri, Tereza
Fu, Xiao
Bates, Paul A.
Khatri, Bhavin S.
Uhlmann, Frank
Fission yeast condensin contributes to interphase chromatin organization and prevents transcription-coupled DNA damage
title Fission yeast condensin contributes to interphase chromatin organization and prevents transcription-coupled DNA damage
title_full Fission yeast condensin contributes to interphase chromatin organization and prevents transcription-coupled DNA damage
title_fullStr Fission yeast condensin contributes to interphase chromatin organization and prevents transcription-coupled DNA damage
title_full_unstemmed Fission yeast condensin contributes to interphase chromatin organization and prevents transcription-coupled DNA damage
title_short Fission yeast condensin contributes to interphase chromatin organization and prevents transcription-coupled DNA damage
title_sort fission yeast condensin contributes to interphase chromatin organization and prevents transcription-coupled dna damage
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643427/
https://www.ncbi.nlm.nih.gov/pubmed/33153481
http://dx.doi.org/10.1186/s13059-020-02183-0
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