酶的调节. 酶的调节. IRBIT是一种新型调节器,用于高等真核生物中的核糖核酸减少酶
Alexei Arnaoutov1, Mary Dasso2
1Laboratory of Gene Regulation and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. arnaouta@mail.nih.gov.
Science (New York, N.Y.)
|September 20, 2014
概括
蛋白质IRBIT通过与核酸减少酶 (RNR) 形成复合物来抑制DNA复制,增强脱氧三酸盐 (dATP) 的抑制. 这种IRBIT-RNR相互作用会影响人类细胞的细胞周期进展.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 核酸减少酶 (RNR) 对于DNA复制和基因组稳定性至关重要,保持平衡的脱氧核酸三酸盐 (dNTP) 池.
- 细胞的RNR是由全性机制调节的,在酵母体中,由Sml1p和Spd1p等小蛋白抑制剂调节.
研究的目的:
- 调查甲基动物蛋白IRBIT在高等真核生物中RNR调节中的作用.
- 阐明IRBIT与RNR活动相互作用并调节的机制.
主要方法:
- 分析了IRBIT和RNR之间的脱氧腺三酸盐 (dATP) 依存复合物的形成.
- 研究人员研究了IRBIT酸化作为复杂形成的调节机制.
- 对dNTP池和细胞周期进展的IRBIT废除的影响在HeLa细胞中进行了评估.
主要成果:
- IRBIT与RNR形成一个dATP依赖的复合体,在酶的活性部位稳定dATP,并抑制RNR.
- 酸化IRBIT调节了RNR-IRBIT复合物的形成.
- 在HeLa细胞中消去IRBIT会导致不平衡的dNTP池和改变细胞周期进展.
结论:
- IRBIT作为元动物中RNR的新型调节剂,增强dATP介导的全抑制作用.
- IRBIT-RNR相互作用为DNA代谢和细胞周期忠实性至关重要的dNTP池提供了新的控制层.
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