核F-actin和myosins驱动异色突破的重新定位
Christopher P Caridi1, Carla D'Agostino1, Taehyun Ryu1
1Department of Molecular and Computational Biology, University of Southern California, Los Angeles, CA, USA.
Nature
|June 22, 2018
概括
科学家们发现核活性纤维和肌蛋白在异色素中移动DNA修复部位. 这种机制确保了双链断裂的安全修复,保持了真核生物的基因组稳定性.
科学领域:
- 细胞生物学
- 分子生物学
- 遗传学
背景情况:
- 具有丰富的重复性DNA的异染色素容易发生子宫外重组.
- 在Drosophila中安全修复异色双链断裂 (DSB) 需要将修复地点转移到核外围.
- 这种转移的分子机制以前是未知的.
研究的目的:
- 阐明负责异色 DSB 修复站点的转移机制.
- 确定参与核内修复部位的定向运动的分子参与者.
主要方法:
- 研究了核活性纤维和相关运动蛋白在DSB修复中的作用.
- 使用Drosophila和小鼠细胞模型研究异性染色体修复过程中的染色体动力学.
- 研究了Arp2/3复合物,核肌蛋白,Smc5/6复合物和Unc45的参与.
主要成果:
- 修复部位的重新定位是由由Arp2/3复合体核化的de novo核性活性纤维的定向运动介导的.
- 与Smc5/6修复复合体及其激活剂Unc45相关的核肌蛋白驱动这种基于actin的运动.
- 在小鼠细胞中,涉及actin核和myosins的已识别的途径被保留并具有异色DSB重新定位的功能.
结论:
- 新型核活性纤维和肌酸是对异色染色体修复至关重要的染色体动态的关键因子.
- 这种机制确保了异染色体的稳定性,并防止了染色体的重新排列.
- 这些发现突出了多细胞真核生物中基因组稳定性的保存途径.
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