作为对机械应力反应的反应,ATR在核外处调节一个检查点
Amit Kumar1, Michele Mazzanti2, Martin Mistrik3
1Fondazione Istituto FIRC di Oncologia Molecolare (IFOM), Via Adamello 16, 20139 Milan, Italy.
Cell
|August 2, 2014
概括
该ATR蛋白对核外的机械应力做出反应,有助于保持染色体的完整性. 这种机械反应对于细胞在物理压力下生存至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 蛋白激酶ATR (阿塔克西亚 - 长生病和Rad3相关) 对于DNA损伤反应和基因组稳定性至关重要.
- 以前的研究表明,酵母Mec1/ATR在DNA复制过程中促进了染色质脱离核外,以防止拓问题.
- 在响应机械力的ATR的作用,独立于DNA损伤,仍然在很大程度上未被探索.
研究的目的:
- 调查ATR活动是否受到核外机械应力的影响.
- 为了确定ATR机械反应的生理相关性和特征.
- 为了阐明ATR缺乏对机械应力反应的后果.
主要方法:
- 免疫光显微镜可视化ATR在人体细胞中的定位.
- 对细胞施加透应力和机械拉伸.
- 在野生型和ATR缺陷细胞中分析细胞周期进展和核包膜完整性.
主要成果:
- 人类ATR在S阶段和前期定位到核外.
- 透应激和机械拉伸诱导ATR在细胞周期中重新定位到细胞核膜.
- ATR的机械反应是可逆的,发生在生理力下,并且独立于DNA损伤信号.
- 缺乏ATR的细胞表现出异常的染色质凝结和核包膜分解.
结论:
- 在核外上,ATR激酶充当机械传感器.
- 机械力量激活ATR,调节核外的可塑性和染色体协会.
- 这种ATR介导的反应有助于细胞适应染色体动力学和核膜扭曲的机械应变.
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