Open AccessNuclear constriction segregates mobile nuclear proteins away from chromatin
Author(s) -
Jerome Irianto,
Charlotte R. Pfeifer,
Rachel R. Bennett,
Yuntao Xia,
Irena L. Ivanovska,
Andrea J. Liu,
Roger A. Greenberg,
Dennis E. Discher
Publication year - 2016
Publication title -
molecular biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.463
H-Index - 225
eISSN - 1939-4586
pISSN - 1059-1524
DOI - 10.1091/mbc.e16-06-0428
Subject(s) - chromatin , biology , heterochromatin , euchromatin , inner membrane , cell nucleus , microbiology and biotechnology , nucleus , nuclease , histone , lamin , dna , genetics , mitochondrion
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.