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Bridging condensins mediate compaction of mitotic chromosomes
Eukaryotic chromosomes compact during mitosis into elongated cylinders—and not the spherical globules expected of self-attracting long flexible polymers. This process is mainly driven by condensin-like proteins. Here, we present Brownian-dynamic simulations involving two types of such proteins with...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10655892/ https://www.ncbi.nlm.nih.gov/pubmed/37976091 http://dx.doi.org/10.1083/jcb.202209113 |
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author | Forte, Giada Boteva, Lora Conforto, Filippo Gilbert, Nick Cook, Peter R. Marenduzzo, Davide |
author_facet | Forte, Giada Boteva, Lora Conforto, Filippo Gilbert, Nick Cook, Peter R. Marenduzzo, Davide |
author_sort | Forte, Giada |
collection | PubMed |
description | Eukaryotic chromosomes compact during mitosis into elongated cylinders—and not the spherical globules expected of self-attracting long flexible polymers. This process is mainly driven by condensin-like proteins. Here, we present Brownian-dynamic simulations involving two types of such proteins with different activities. One, which we refer to as looping condensins, anchors long-lived chromatin loops to create bottlebrush structures. The second, referred to as bridging condensins, forms multivalent bridges between distant parts of these loops. We show that binding of bridging condensins leads to the formation of shorter and stiffer mitotic-like cylinders without requiring any additional energy input. These cylinders have several features matching experimental observations. For instance, the axial condensin backbone breaks up into clusters as found by microscopy, and cylinder elasticity qualitatively matches that seen in chromosome pulling experiments. Additionally, simulating global condensin depletion or local faulty condensin loading gives phenotypes seen experimentally and points to a mechanistic basis for the structure of common fragile sites in mitotic chromosomes. |
format | Online Article Text |
id | pubmed-10655892 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-106558922023-11-17 Bridging condensins mediate compaction of mitotic chromosomes Forte, Giada Boteva, Lora Conforto, Filippo Gilbert, Nick Cook, Peter R. Marenduzzo, Davide J Cell Biol Article Eukaryotic chromosomes compact during mitosis into elongated cylinders—and not the spherical globules expected of self-attracting long flexible polymers. This process is mainly driven by condensin-like proteins. Here, we present Brownian-dynamic simulations involving two types of such proteins with different activities. One, which we refer to as looping condensins, anchors long-lived chromatin loops to create bottlebrush structures. The second, referred to as bridging condensins, forms multivalent bridges between distant parts of these loops. We show that binding of bridging condensins leads to the formation of shorter and stiffer mitotic-like cylinders without requiring any additional energy input. These cylinders have several features matching experimental observations. For instance, the axial condensin backbone breaks up into clusters as found by microscopy, and cylinder elasticity qualitatively matches that seen in chromosome pulling experiments. Additionally, simulating global condensin depletion or local faulty condensin loading gives phenotypes seen experimentally and points to a mechanistic basis for the structure of common fragile sites in mitotic chromosomes. Rockefeller University Press 2023-11-17 /pmc/articles/PMC10655892/ /pubmed/37976091 http://dx.doi.org/10.1083/jcb.202209113 Text en © 2023 Forte et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Forte, Giada Boteva, Lora Conforto, Filippo Gilbert, Nick Cook, Peter R. Marenduzzo, Davide Bridging condensins mediate compaction of mitotic chromosomes |
title | Bridging condensins mediate compaction of mitotic chromosomes |
title_full | Bridging condensins mediate compaction of mitotic chromosomes |
title_fullStr | Bridging condensins mediate compaction of mitotic chromosomes |
title_full_unstemmed | Bridging condensins mediate compaction of mitotic chromosomes |
title_short | Bridging condensins mediate compaction of mitotic chromosomes |
title_sort | bridging condensins mediate compaction of mitotic chromosomes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10655892/ https://www.ncbi.nlm.nih.gov/pubmed/37976091 http://dx.doi.org/10.1083/jcb.202209113 |
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