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Theory and simulations of condensin mediated loop extrusion in DNA
Condensation of hundreds of mega-base-pair-long human chromosomes in a small nuclear volume is a spectacular biological phenomenon. This process is driven by the formation of chromosome loops. The ATP consuming motor, condensin, interacts with chromatin segments to actively extrude loops. Motivated...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497514/ https://www.ncbi.nlm.nih.gov/pubmed/34620869 http://dx.doi.org/10.1038/s41467-021-26167-1 |
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author | Takaki, Ryota Dey, Atreya Shi, Guang Thirumalai, D. |
author_facet | Takaki, Ryota Dey, Atreya Shi, Guang Thirumalai, D. |
author_sort | Takaki, Ryota |
collection | PubMed |
description | Condensation of hundreds of mega-base-pair-long human chromosomes in a small nuclear volume is a spectacular biological phenomenon. This process is driven by the formation of chromosome loops. The ATP consuming motor, condensin, interacts with chromatin segments to actively extrude loops. Motivated by real-time imaging of loop extrusion (LE), we created an analytically solvable model, predicting the LE velocity and step size distribution as a function of external load. The theory fits the available experimental data quantitatively, and suggests that condensin must undergo a large conformational change, induced by ATP binding, bringing distant parts of the motor to proximity. Simulations using a simple model confirm that the motor transitions between an open and a closed state in order to extrude loops by a scrunching mechanism, similar to that proposed in DNA bubble formation during bacterial transcription. Changes in the orientation of the motor domains are transmitted over ~50 nm, connecting the motor head and the hinge, thus providing an allosteric basis for LE. |
format | Online Article Text |
id | pubmed-8497514 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-84975142021-10-22 Theory and simulations of condensin mediated loop extrusion in DNA Takaki, Ryota Dey, Atreya Shi, Guang Thirumalai, D. Nat Commun Article Condensation of hundreds of mega-base-pair-long human chromosomes in a small nuclear volume is a spectacular biological phenomenon. This process is driven by the formation of chromosome loops. The ATP consuming motor, condensin, interacts with chromatin segments to actively extrude loops. Motivated by real-time imaging of loop extrusion (LE), we created an analytically solvable model, predicting the LE velocity and step size distribution as a function of external load. The theory fits the available experimental data quantitatively, and suggests that condensin must undergo a large conformational change, induced by ATP binding, bringing distant parts of the motor to proximity. Simulations using a simple model confirm that the motor transitions between an open and a closed state in order to extrude loops by a scrunching mechanism, similar to that proposed in DNA bubble formation during bacterial transcription. Changes in the orientation of the motor domains are transmitted over ~50 nm, connecting the motor head and the hinge, thus providing an allosteric basis for LE. Nature Publishing Group UK 2021-10-07 /pmc/articles/PMC8497514/ /pubmed/34620869 http://dx.doi.org/10.1038/s41467-021-26167-1 Text en © The Author(s) 2021 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Takaki, Ryota Dey, Atreya Shi, Guang Thirumalai, D. Theory and simulations of condensin mediated loop extrusion in DNA |
title | Theory and simulations of condensin mediated loop extrusion in DNA |
title_full | Theory and simulations of condensin mediated loop extrusion in DNA |
title_fullStr | Theory and simulations of condensin mediated loop extrusion in DNA |
title_full_unstemmed | Theory and simulations of condensin mediated loop extrusion in DNA |
title_short | Theory and simulations of condensin mediated loop extrusion in DNA |
title_sort | theory and simulations of condensin mediated loop extrusion in dna |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497514/ https://www.ncbi.nlm.nih.gov/pubmed/34620869 http://dx.doi.org/10.1038/s41467-021-26167-1 |
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