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: Edward J. Banigan, Leonid A. Mirny
Format: Article
Language:English
Published: American Physical Society 2019-07-01
Series:Physical Review X
Online Access:http://doi.org/10.1103/PhysRevX.9.031007
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author Edward J. Banigan
Leonid A. Mirny
author_facet Edward J. Banigan
Leonid A. Mirny
author_sort Edward J. Banigan
collection DOAJ
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 doaj.art-36488806a02e493bacfc702fb06785872022-12-21T21:30:37ZengAmerican Physical SocietyPhysical Review X2160-33082019-07-019303100710.1103/PhysRevX.9.031007Limits of Chromosome Compaction by Loop-Extruding MotorsEdward J. BaniganLeonid A. MirnyDuring 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.http://doi.org/10.1103/PhysRevX.9.031007
spellingShingle Edward J. Banigan
Leonid A. Mirny
Limits of Chromosome Compaction by Loop-Extruding Motors
Physical Review X
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 http://doi.org/10.1103/PhysRevX.9.031007
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