期刊
MOLECULAR BIOLOGY OF THE CELL
卷 27, 期 25, 页码 4011-4020出版社
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E16-06-0428
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资金
- Direct For Mathematical & Physical Scien
- Division Of Materials Research [1506625] Funding Source: National Science Foundation
- Division Of Materials Research
- Direct For Mathematical & Physical Scien [1359351] Funding Source: National Science Foundation
- NCI NIH HHS [U54 CA193417] Funding Source: Medline
- NIGMS NIH HHS [R01 GM101149] Funding Source: Medline
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.
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