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异色素驱动的核软化保护基因组免受机械压力引起的损伤

Michele M Nava¹, Yekaterina A Miroshnikova¹, Leah C Biggs²

¹Helsinki Institute of Life Science, Biomedicum Helsinki, University of Helsinki, 00290 Helsinki, Finland; Wihuri Research Institute, Biomedicum Helsinki, University of Helsinki, 00290 Helsinki, Finland; Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland; Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany; Cologne Excellence Cluster for Stress Responses in Ageing-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.

|April 18, 2020

概括

细胞通过染色质变化使其核变软,从而保护它们的基因组免受机械压力. 组织也通过调整来减少力量,防止DNA损伤和维持平衡.

科学领域:

细胞生物学
生物物理
基因组学

背景情况:

组织平衡依赖于在机械应力下保持功能完整性.
保护基因组免受作用于细胞和细胞核的机械力量的机制尚未完全理解.

研究的目的:

研究细胞和组织如何保护基因组免受机械压力.
阐明核力学和染色质在基因组保护中的作用.

主要方法:

对细胞和组织施加的机械拉伸.
核变形和染色质状态的分析 (H3K9me3).
对DNA损伤和组织规模反应的评估.

主要成果:

机械拉伸使核变形,最初由于H3K9me3-异色素的损失而变软.
核软化改变了染色体的整体结构,
不能使核变软会导致DNA受损.
高幅度拉伸会诱导细胞上组织调整以重新分配力.
组织尺度上的适应涉及细胞间接触,并关闭核机制传导.

结论:

染色体在改变其机械状态以保持基因组完整性方面发挥着非常规的作用.
细胞采用核和组织层面的机制来应对机械变形.
这些机械反应对于防止DNA损伤和在压力下确保组织平衡至关重要.

关键词:

发生DNA损伤染色体不同染色素机械保护机械传导核架构核膜核力学干细胞

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