神经菌检查点激酶2:是昼夜和细胞周期之间的调节性联系
António M Pregueiro1, Qiuyun Liu, Christopher L Baker
1Department of Genetics, Dartmouth Medical School, Hanover, NH 03755, USA.
Science (New York, N.Y.)
|July 1, 2006
概括
神经的时钟基因期-4 (prd-4),是Chk2的正统基因,将昼夜节律与DNA损伤反应联系起来. PRD-4通过酸化FRQ来调节时钟输出,影响细胞周期和时钟重置.
科学领域:
- 循环生物学的日间生物.
- 分子遗传学 分子遗传学
- 细胞周期调节细胞周期调节
背景情况:
- 昼夜时钟调节了每天的生物节奏.
- 了解外部因素如DNA损伤如何影响昼夜时间至关重要.
- 特定基因在整合这些途径中的作用尚未完全理解.
研究的目的:
- 为了识别和描述参与神经细胞中昼夜钟调节的新型基因.
- 调查昼夜时钟和DNA损伤反应途径之间的功能关系.
- 阐明PRD-4影响昼夜输出和输入的分子机制.
主要方法:
- 基因查和定位克隆以确定prd-4基因.
- 生物化学测试以确定PRD-4与FRQ的相互作用及其酶活性.
- 在不同的条件下分析prd-4表达模式.
- 研究DNA破坏性物质对野生型和prd-4突变菌株的昼夜时钟的影响.
主要成果:
- 确定了周期-4 (prd-4) 基因,其产物PRD-4是哺乳动物检查点激酶2 (Chk2) 的正义基因.
- PRD-4在物理上与昼夜时钟组成部分FRQ相互作用,促进其酸化.
- prd-4的表达是由昼夜时钟调节的.
- 破坏DNA的毒剂以日间时间的依赖方式重置昼夜时钟,这一过程需要PRD-4.
结论:
- prd-4,神经子Chk2的正统,建立了一个分子链接,在昼夜输出和输入路径之间.
- PRD-4有条件地从昼夜输出回,以影响时钟输入和细胞周期进展.
- 这项研究揭示了一种新的机制,将昼夜定时与DNA损伤监测相结合.
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