Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Forte, Giada, Boteva, Lora, Conforto, Filippo, Gilbert, Nick, Cook, Peter R., Marenduzzo, Davide
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2023
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
_version_ 1785147997434150912
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
work_keys_str_mv AT fortegiada bridgingcondensinsmediatecompactionofmitoticchromosomes
AT botevalora bridgingcondensinsmediatecompactionofmitoticchromosomes
AT confortofilippo bridgingcondensinsmediatecompactionofmitoticchromosomes
AT gilbertnick bridgingcondensinsmediatecompactionofmitoticchromosomes
AT cookpeterr bridgingcondensinsmediatecompactionofmitoticchromosomes
AT marenduzzodavide bridgingcondensinsmediatecompactionofmitoticchromosomes