在复制性酶激活中,二维DONSON的结构机制
Milos A Cvetkovic1, Paolo Passaretti2, Agata Butryn1
1Macromolecular Machines Laboratory, The Francis Crick Institute, London NW1 1AT, UK.
Molecular cell
|October 11, 2023
概括
孙的下游邻居 (DONSON) 桥梁双重CMG复合体,重新配置DNA复制的MCM电机. 唐森突变损害了GINS/MCM相互作用和DNA合成,影响人类细胞和Xenopus蛋提取物.
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:
- 复制螺旋酶CMG组件对于DNA复制启动至关重要.
- 虽然酵母CMG的形成是可以理解的,但其在更高的真核生物中的机制仍然不清楚.
- 甲基动物DONSON将GINS传递给MCM,但其在CMG组装中的作用尚不清楚.
研究的目的:
- 为了研究DONSON在CMG组装过程中对MCM双六合体的影响,在更高的真核生物中.
- 为了阐明由DONSON介导的CMG形成的结构机制.
主要方法:
- 从Xenopus蛋提取物中提取的蛋白质的冷电子显微镜 (cryo-EM).
- 对DONSON二分化及其对GINS和MCM相互作用的影响的分析.
主要成果:
- 在Xenopus提取物中确定了一种双重CMG复合体,由DONSON二元体桥接.
- DONSON连接元件对于复制是必不可少的.
- 唐森在双重CMG综合体内重新配置了MCM电机.
- 唐森二元化突变破坏了GINS/MCM参与和DNA合成.
结论:
- 唐森在高真核细胞CMG酶形成中发挥着关键作用,通过桥接MCM双六合体.
- 唐松的结构作用对DNA复制至关重要,其功能障碍是某些人类遗传疾病的基础.
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