Encounter times of chromatin loci influenced by polymer decondensation
The time for a DNA sequence to find its homologous counterpart depends on a long random search inside the cell nucleus. Using polymer models, we compute here the mean first encounter time (MFET) between two sites located on two different polymer chains and confined locally by potential wells. We fin...
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Language: | English |
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American Physical Society
2018
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Online Access: | http://hdl.handle.net/1721.1/114509 https://orcid.org/0000-0002-8594-6529 |
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author | Holcman, D. Amitai, Assaf |
author2 | Institute for Medical Engineering and Science |
author_facet | Institute for Medical Engineering and Science Holcman, D. Amitai, Assaf |
author_sort | Holcman, D. |
collection | MIT |
description | The time for a DNA sequence to find its homologous counterpart depends on a long random search inside the cell nucleus. Using polymer models, we compute here the mean first encounter time (MFET) between two sites located on two different polymer chains and confined locally by potential wells. We find that reducing tethering forces acting on the polymers results in local decondensation, and numerical simulations of the polymer model show that these changes are associated with a reduction of the MFET by several orders of magnitude. We derive here new asymptotic formula for the MFET, confirmed by Brownian simulations. We conclude from the present modeling approach that the fast search for homology is mediated by a local chromatin decondensation due to the release of multiple chromatin tethering forces. The present scenario could explain how the homologous recombination pathway for double-stranded DNA repair is controlled by its random search step. |
first_indexed | 2024-09-23T15:43:45Z |
format | Article |
id | mit-1721.1/114509 |
institution | Massachusetts Institute of Technology |
language | English |
last_indexed | 2024-09-23T15:43:45Z |
publishDate | 2018 |
publisher | American Physical Society |
record_format | dspace |
spelling | mit-1721.1/1145092022-10-02T03:43:54Z Encounter times of chromatin loci influenced by polymer decondensation Holcman, D. Amitai, Assaf Institute for Medical Engineering and Science Massachusetts Institute of Technology. Department of Chemical Engineering Amitai, Assaf The time for a DNA sequence to find its homologous counterpart depends on a long random search inside the cell nucleus. Using polymer models, we compute here the mean first encounter time (MFET) between two sites located on two different polymer chains and confined locally by potential wells. We find that reducing tethering forces acting on the polymers results in local decondensation, and numerical simulations of the polymer model show that these changes are associated with a reduction of the MFET by several orders of magnitude. We derive here new asymptotic formula for the MFET, confirmed by Brownian simulations. We conclude from the present modeling approach that the fast search for homology is mediated by a local chromatin decondensation due to the release of multiple chromatin tethering forces. The present scenario could explain how the homologous recombination pathway for double-stranded DNA repair is controlled by its random search step. 2018-04-03T17:00:32Z 2018-04-03T17:00:32Z 2018-03 2018-02 2018-03-27T18:00:15Z Article http://purl.org/eprint/type/JournalArticle 2470-0045 2470-0053 http://hdl.handle.net/1721.1/114509 Amitai, A. and D. Holcman. "Encounter times of chromatin loci influenced by polymer decondensation." Physical Review E 97, 3 (March 2018): 032417 © 2018 American Physical Society https://orcid.org/0000-0002-8594-6529 en http://dx.doi.org/10.1103/PhysRevE.97.032417 Physical Review E Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. American Physical Society application/pdf American Physical Society American Physical Society |
spellingShingle | Holcman, D. Amitai, Assaf Encounter times of chromatin loci influenced by polymer decondensation |
title | Encounter times of chromatin loci influenced by polymer decondensation |
title_full | Encounter times of chromatin loci influenced by polymer decondensation |
title_fullStr | Encounter times of chromatin loci influenced by polymer decondensation |
title_full_unstemmed | Encounter times of chromatin loci influenced by polymer decondensation |
title_short | Encounter times of chromatin loci influenced by polymer decondensation |
title_sort | encounter times of chromatin loci influenced by polymer decondensation |
url | http://hdl.handle.net/1721.1/114509 https://orcid.org/0000-0002-8594-6529 |
work_keys_str_mv | AT holcmand encountertimesofchromatinlociinfluencedbypolymerdecondensation AT amitaiassaf encountertimesofchromatinlociinfluencedbypolymerdecondensation |