Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Irianto, Jerome, Pfeifer, Charlotte R., Bennett, Rachel R., Xia, Yuntao, Ivanovska, Irena L., Liu, Andrea J., Greenberg, Roger A., Discher, Dennis E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
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
_version_ 1782481282318467072
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
work_keys_str_mv AT iriantojerome nuclearconstrictionsegregatesmobilenuclearproteinsawayfromchromatin
AT pfeifercharlotter nuclearconstrictionsegregatesmobilenuclearproteinsawayfromchromatin
AT bennettrachelr nuclearconstrictionsegregatesmobilenuclearproteinsawayfromchromatin
AT xiayuntao nuclearconstrictionsegregatesmobilenuclearproteinsawayfromchromatin
AT ivanovskairenal nuclearconstrictionsegregatesmobilenuclearproteinsawayfromchromatin
AT liuandreaj nuclearconstrictionsegregatesmobilenuclearproteinsawayfromchromatin
AT greenbergrogera nuclearconstrictionsegregatesmobilenuclearproteinsawayfromchromatin
AT discherdennise nuclearconstrictionsegregatesmobilenuclearproteinsawayfromchromatin