损坏的tRNA核出口链接DNA损伤和细胞循环检查点
Ata Ghavidel1, Thomas Kislinger, Oxana Pogoutse
1Ontario Cancer Institute, Division of Signaling Biology, Toronto, Ontario M5G-1L7, Canada. aghavide@uhnres.utoronto.ca
Cell
|November 30, 2007
概括
DNA损伤触发了酵母中未连接转移RNA (tRNA) 的核积累,通过信号通路进行介导. 这会影响细胞循环停止和基因组完整性.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- 细胞激活复杂的反应,以在基因毒性压力下保持基因组完整性.
- 转移RNA (tRNA) 生物发生和核细胞质贩运对于蛋白质合成和细胞功能至关重要.
研究的目的:
- 为了研究未连接的tRNA积累在酵母对DNA损伤的反应中的作用.
- 阐明调节tRNA核出口的分子机制及其对细胞循环进展的影响.
主要方法:
- 使用的酵母Saccharomyces cerevisiae模型系统.
- 研究了DNA损伤反应途径,包括MEC1和RAD53.
- 分析了tRNA核细胞质贩运和Gcn4转录因子激活.
主要成果:
- 在DNA损伤后,在酵母核中观察到未连接的tRNA的快速积累.
- 证明了MEC1-和RAD53-依赖的内子含有tRNA的核出口的抑制.
- 表明核未连接tRNA激活Gcn4,通过延迟Cln2积累促进G1细胞周期的停止.
结论:
- 调节的核细胞质tRNA贩运是对DNA损伤的不可或缺的适应.
- tRNA贩运,蛋白质合成和检查点执行之间的交叉声功能性地结合了tRNA生物发生和细胞循环进展.
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