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核力学的调控及其对 DNA 损伤的影响。

Regulation of Nuclear Mechanics and the Impact on DNA Damage.

机构信息

Department of Oncology and Metabolism, University of Sheffield, Sheffield S10 2RX, UK.

Insigneo Institute for in Silico Medicine, University of Sheffield, Sheffield S10 2RX, UK.

出版信息

Int J Mol Sci. 2021 Mar 20;22(6):3178. doi: 10.3390/ijms22063178.

DOI:10.3390/ijms22063178
PMID:33804722
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8003950/
Abstract

In eukaryotic cells, the nucleus houses the genomic material of the cell. The physical properties of the nucleus and its ability to sense external mechanical cues are tightly linked to the regulation of cellular events, such as gene expression. Nuclear mechanics and morphology are altered in many diseases such as cancer and premature ageing syndromes. Therefore, it is important to understand how different components contribute to nuclear processes, organisation and mechanics, and how they are misregulated in disease. Although, over the years, studies have focused on the nuclear lamina-a mesh of intermediate filament proteins residing between the chromatin and the nuclear membrane-there is growing evidence that chromatin structure and factors that regulate chromatin organisation are essential contributors to the physical properties of the nucleus. Here, we review the main structural components that contribute to the mechanical properties of the nucleus, with particular emphasis on chromatin structure. We also provide an example of how nuclear stiffness can both impact and be affected by cellular processes such as DNA damage and repair.

摘要

在真核细胞中,细胞核容纳着细胞的基因组物质。细胞核的物理性质及其感知外部机械线索的能力与细胞事件的调节密切相关,如基因表达。在许多疾病中,如癌症和早衰综合征,核力学和形态发生了改变。因此,了解不同的成分如何有助于核过程、组织和力学,以及它们在疾病中是如何失调的,这一点很重要。尽管多年来,研究一直集中在核纤层上——一种位于染色质和核膜之间的中间丝蛋白网格上——但越来越多的证据表明,染色质结构和调节染色质组织的因素是细胞核物理性质的重要贡献者。在这里,我们回顾了有助于细胞核机械性能的主要结构成分,特别强调了染色质结构。我们还提供了一个例子,说明核硬度如何既能影响又能受到细胞过程的影响,如 DNA 损伤和修复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8f1/8003950/f72bf7f1c489/ijms-22-03178-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8f1/8003950/a7dcb26ca379/ijms-22-03178-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8f1/8003950/f2f86b8ce67e/ijms-22-03178-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8f1/8003950/f72bf7f1c489/ijms-22-03178-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8f1/8003950/a7dcb26ca379/ijms-22-03178-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8f1/8003950/f2f86b8ce67e/ijms-22-03178-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8f1/8003950/f72bf7f1c489/ijms-22-03178-g003.jpg

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Liquid chromatin Hi-C characterizes compartment-dependent chromatin interaction dynamics.液体染色质 Hi-C 描绘了依赖区室的染色质互作动力学。
疾病脑类器官模型中细胞外基质结构改变及硬度升高
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Actin from within - how nuclear myosins and actin regulate nuclear architecture and mechanics.来自内部的肌动蛋白——核肌球蛋白和肌动蛋白如何调节核结构与力学
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The transmembrane protein Syndecan is required for stem cell survival and maintenance of their nuclear properties.跨膜蛋白Syndecan是干细胞存活及其核特性维持所必需的。
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