活细胞成像揭示了端粒酶招募到端粒的动态
Jens C Schmidt1, Arthur J Zaug1, Thomas R Cech1
1Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, BioFrontiers Institute, University of Colorado Boulder, Boulder, CO 80309, USA.
Cell
|August 16, 2016
概括
在癌细胞中对基因组完整性至关重要的端粒酶通过快速3D扩散被招募到端粒中. 它的稳定关联取决于TERT和TPP1的相互作用,显示出动态的招募机制.
科学领域:
- 分子生物学
- 细胞生物学
- 遗传学
背景情况:
- 端粒酶通过在染色体末端添加DNA重复来维持基因组完整性.
- 活跃的细胞分裂是90%的癌症的特征,依赖于端粒酶功能.
- 在细胞循环的S阶段,对端粒酶招募的精确分子机制尚不完全理解.
研究的目的:
- 阐明人类端粒酶贩运和在活细胞中招募端粒的分子机制.
- 研究细胞周期中端粒酶和端粒之间的动态相互作用.
主要方法:
- 用CRISPR编辑基因组来操纵细胞组件.
- 使用单分子成像技术追踪活人细胞核中的端粒酶运动.
主要成果:
- 端粒酶利用三维扩散来定位端粒,它们的相互作用是暂时的,很少形成稳定的结合.
- 短暂的和稳定的端粒关联都通过端粒酶蛋白TERT和端粒蛋白TPP1之间的直接相互作用进行介导.
- 端粒酶招募是由扩散端粒酶和染色体末端之间的动态相互作用驱动的.
结论:
- 端粒酶对端粒的招募是一个由扩散和特定蛋白质相互作用控制的动态过程.
- 了解这些机制可以了解基因组完整性和潜在的癌症治疗点.
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