Limits of Chromosome Compaction by Loop-Extruding Motors

During mitosis, human chromosomes are linearly compacted about 1000-fold by loop-extruding motors. Recent experiments have shown that condensins extrude DNA loops but in a “one-sided” manner. This contrasts with existing models, which predict that symmetric, “two-sided” loop extrusion accounts for m...

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Main Authors: Banigan, Edward J, Mirny, Leonid A
Other Authors: Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Format: Article
Language:English
Published: American Physical Society (APS) 2020
Online Access:https://hdl.handle.net/1721.1/126349
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author Banigan, Edward J
Mirny, Leonid A
author2 Massachusetts Institute of Technology. Institute for Medical Engineering & Science
author_facet Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Banigan, Edward J
Mirny, Leonid A
author_sort Banigan, Edward J
collection MIT
description During mitosis, human chromosomes are linearly compacted about 1000-fold by loop-extruding motors. Recent experiments have shown that condensins extrude DNA loops but in a “one-sided” manner. This contrasts with existing models, which predict that symmetric, “two-sided” loop extrusion accounts for mitotic chromosome compaction. We explore whether one-sided extrusion, as it is currently seen in experiments, can compact chromosomes by developing a mean-field theoretical model for polymer compaction by motors that actively extrude loops and dynamically turnover. The model establishes a stringent upper bound of only about tenfold for compaction by strictly one-sided extrusion. We confirm this result with stochastic simulations. Thus, strictly one-sided extrusion as it has been observed so far cannot be the sole mechanism of chromosome compaction. However, as shown by the model, other two-sided or effectively two-sided mechanisms can achieve sufficient compaction.
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spelling mit-1721.1/1263492022-10-01T06:12:24Z Limits of Chromosome Compaction by Loop-Extruding Motors Banigan, Edward J Mirny, Leonid A Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Physics During mitosis, human chromosomes are linearly compacted about 1000-fold by loop-extruding motors. Recent experiments have shown that condensins extrude DNA loops but in a “one-sided” manner. This contrasts with existing models, which predict that symmetric, “two-sided” loop extrusion accounts for mitotic chromosome compaction. We explore whether one-sided extrusion, as it is currently seen in experiments, can compact chromosomes by developing a mean-field theoretical model for polymer compaction by motors that actively extrude loops and dynamically turnover. The model establishes a stringent upper bound of only about tenfold for compaction by strictly one-sided extrusion. We confirm this result with stochastic simulations. Thus, strictly one-sided extrusion as it has been observed so far cannot be the sole mechanism of chromosome compaction. However, as shown by the model, other two-sided or effectively two-sided mechanisms can achieve sufficient compaction. NSF Physics of Living Systems (Grant 15049420) National Institutes of Health (Grant GM114190) National Institutes of Health (Grant DK107980) 2020-07-23T16:11:02Z 2020-07-23T16:11:02Z 2019-07 2019-02 2019-10-09T16:56:52Z Article http://purl.org/eprint/type/JournalArticle 2160-3308 https://hdl.handle.net/1721.1/126349 Banigan, Edward J. and Leonid A. Mirny. "Limits of Chromosome Compaction by Loop-Extruding Motors." Physical Review X 9, 3 (July 2019): 031007 en 10.1103/physrevx.9.031007 Physical Review X Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf American Physical Society (APS) APS
spellingShingle Banigan, Edward J
Mirny, Leonid A
Limits of Chromosome Compaction by Loop-Extruding Motors
title Limits of Chromosome Compaction by Loop-Extruding Motors
title_full Limits of Chromosome Compaction by Loop-Extruding Motors
title_fullStr Limits of Chromosome Compaction by Loop-Extruding Motors
title_full_unstemmed Limits of Chromosome Compaction by Loop-Extruding Motors
title_short Limits of Chromosome Compaction by Loop-Extruding Motors
title_sort limits of chromosome compaction by loop extruding motors
url https://hdl.handle.net/1721.1/126349
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