DNA损伤会导致ATM依赖的异染色素损失,导致核软化,斑点和破裂
Nebiyat Eskndir1, Manseeb Hossain1, Marilena L Currey1
1Biology Department, University of Massachusetts Amherst, Amherst, MA.
bioRxiv : the preprint server for biology
|June 10, 2024
概括
DNA损伤使核变软,增加了声和破裂. 这种依赖于ATM的过程涉及异色染色素的损失,影响了核的完整性和功能.
科学领域:
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
- 遗传学 遗传学 是一个
背景情况:
- 核性对细胞功能至关重要,缺陷与衰老,心脏病和癌症有关.
- 核泡和核破裂,通常是由核形状的损失引起的,导致DNA损伤和功能障碍.
- 增加的DNA损伤对核物理性质的影响在很大程度上仍未被探索.
研究的目的:
- 为了研究DNA损伤如何影响核度,形状和破裂.
- 为了确定DNA损伤是否可以诱导影响核完整性的负反循环.
主要方法:
- MEF细胞被用破坏DNA的药物 (cisplatin,白素) 治疗.
- 通过显微镜观察到核喷射和破裂.
- 微操纵力测量评估了核力学.
- 免疫光测量了异染色体变化和ATM通路激活.
主要成果:
- DNA损伤诱导了快速的核声和相间细胞的破裂.
- 观察到核软化,特别是基于色素的力学减少.
- 确定了ATM依赖于异性染色素的丧失作为机制.
- 抑制ATM可以挽救观察到的核缺陷.
结论:
- DNA 损伤触发了一条依赖于ATM的途径,导致异染色素的损失.
- 这种损失会使核变软,导致声和破裂.
- 这些发现揭示了一个新的机制,将DNA损伤与改变的核力学和完整性联系在一起.
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