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Nuclear constriction segregates mobile nuclear proteins away from chromatin
As a cell squeezes its nucleus through adjacent tissue, penetrates a basement membrane, or enters a small blood capillary, chromatin density and nuclear factors could in principle be physically perturbed. Here, in cancer cell migration through rigid micropores and in passive pulling into micropipett...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5156542/ https://www.ncbi.nlm.nih.gov/pubmed/27798234 http://dx.doi.org/10.1091/mbc.E16-06-0428 |
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author | Irianto, Jerome Pfeifer, Charlotte R. Bennett, Rachel R. Xia, Yuntao Ivanovska, Irena L. Liu, Andrea J. Greenberg, Roger A. Discher, Dennis E. |
author_facet | Irianto, Jerome Pfeifer, Charlotte R. Bennett, Rachel R. Xia, Yuntao Ivanovska, Irena L. Liu, Andrea J. Greenberg, Roger A. Discher, Dennis E. |
author_sort | Irianto, Jerome |
collection | PubMed |
description | As a cell squeezes its nucleus through adjacent tissue, penetrates a basement membrane, or enters a small blood capillary, chromatin density and nuclear factors could in principle be physically perturbed. Here, in cancer cell migration through rigid micropores and in passive pulling into micropipettes, local compaction of chromatin is observed coincident with depletion of mobile factors. Heterochromatin/euchromatin was previously estimated from molecular mobility measurements to occupy a volume fraction f of roughly two-thirds of the nuclear volume, but based on the relative intensity of DNA and histones in several cancer cell lines drawn into narrow constrictions, f can easily increase locally to nearly 100%. By contrast, mobile proteins in the nucleus, including a dozen that function as DNA repair proteins (e.g., BRCA1, 53BP1) or nucleases (e.g., Cas9, FokI), are depleted within the constriction, approaching 0%. Such losses—compounded by the occasional rupture of the nuclear envelope—can have important functional consequences. Studies of a nuclease that targets a locus in chromosome-1 indeed show that constricted migration delays DNA damage. |
format | Online Article Text |
id | pubmed-5156542 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-51565422017-03-02 Nuclear constriction segregates mobile nuclear proteins away from chromatin Irianto, Jerome Pfeifer, Charlotte R. Bennett, Rachel R. Xia, Yuntao Ivanovska, Irena L. Liu, Andrea J. Greenberg, Roger A. Discher, Dennis E. Mol Biol Cell Articles As a cell squeezes its nucleus through adjacent tissue, penetrates a basement membrane, or enters a small blood capillary, chromatin density and nuclear factors could in principle be physically perturbed. Here, in cancer cell migration through rigid micropores and in passive pulling into micropipettes, local compaction of chromatin is observed coincident with depletion of mobile factors. Heterochromatin/euchromatin was previously estimated from molecular mobility measurements to occupy a volume fraction f of roughly two-thirds of the nuclear volume, but based on the relative intensity of DNA and histones in several cancer cell lines drawn into narrow constrictions, f can easily increase locally to nearly 100%. By contrast, mobile proteins in the nucleus, including a dozen that function as DNA repair proteins (e.g., BRCA1, 53BP1) or nucleases (e.g., Cas9, FokI), are depleted within the constriction, approaching 0%. Such losses—compounded by the occasional rupture of the nuclear envelope—can have important functional consequences. Studies of a nuclease that targets a locus in chromosome-1 indeed show that constricted migration delays DNA damage. The American Society for Cell Biology 2016-12-15 /pmc/articles/PMC5156542/ /pubmed/27798234 http://dx.doi.org/10.1091/mbc.E16-06-0428 Text en © 2016 Irianto, Pfeifer, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. |
spellingShingle | Articles Irianto, Jerome Pfeifer, Charlotte R. Bennett, Rachel R. Xia, Yuntao Ivanovska, Irena L. Liu, Andrea J. Greenberg, Roger A. Discher, Dennis E. Nuclear constriction segregates mobile nuclear proteins away from chromatin |
title | Nuclear constriction segregates mobile nuclear proteins away from chromatin |
title_full | Nuclear constriction segregates mobile nuclear proteins away from chromatin |
title_fullStr | Nuclear constriction segregates mobile nuclear proteins away from chromatin |
title_full_unstemmed | Nuclear constriction segregates mobile nuclear proteins away from chromatin |
title_short | Nuclear constriction segregates mobile nuclear proteins away from chromatin |
title_sort | nuclear constriction segregates mobile nuclear proteins away from chromatin |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5156542/ https://www.ncbi.nlm.nih.gov/pubmed/27798234 http://dx.doi.org/10.1091/mbc.E16-06-0428 |
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