转录沉默和长寿蛋白Sir2是一种依赖NAD的基因组脱乙酶
S Imai1, C M Armstrong, M Kaeberlein
1Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Nature
|February 29, 2000
概括
酵母Sir2是一种基因素脱乙酶,通过从基因素中去除乙基来使基因沉默并延长寿命. 这种依赖NAD的脱乙烯化与新陈代谢,基因沉默和衰老有关.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物化学 生物化学
背景情况:
- 酵母Sir2是异色素蛋白的关键组成部分,调节基因沉默,重组和寿命.
- 基因组H3和H4上的特定溶酶对沉默至关重要,乙化模式与活性或沉默的染色质相关.
- Sir2的过度表达导致了全球素脱甲基化,这表明它作为素脱甲基酶的作用.
研究的目的:
- 为了研究酵母和小鼠Sir2蛋白的酶活性.
- 为了确定特定的质子标和尼古丁胺胺二核酸 (NAD) 在Sir2的脱乙酶活性中的作用.
- 将Sir2的脱乙酶功能与其在静音,重组抑制和寿命延长中的体内作用联系起来.
主要方法:
- 生物化学测试以测量基因素脱乙酶活性.
- 酵母和小鼠Sir2蛋白质的分析.
- 对SIR2基因的突变分析.
- 评估基因沉默,重组和复制寿命的体内研究.
主要成果:
- 酵母和小鼠Sir2蛋白质作为NAD依赖的基因组脱乙酶起作用.
- Sir2 特别去乙化素 H3 基因素的 lysines 9 和 14,以及 H4 基因素的 lysine 16.
- 在SIR2中发生的突变会损害其去乙酶活性,与沉默,重组抑制和寿命延长的缺陷相关.
结论:
- Sir2在酵母中依赖NAD的基因组脱乙酶活性对于其在酵母中的生物功能至关重要.
- 这种机制提供了新陈代谢,基因组沉默和衰老之间的分子联系.
- 这些发现可能会延伸到更高的真核生物,这表明NAD依赖脱甲基化有保留的作用.
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