人类的复制前综合体是一个开放的综合体
Jian Li1, Jiangqing Dong2, Weitao Wang3
1School of Biological Sciences, The University of Hong Kong, Hong Kong, China.
Cell
|January 7, 2023
概括
研究人员发现微染色体维护 (MCM) 双六合体 (DH) 如何通过溶解DNA链来启动DNA复制. 这种结构揭示了人类细胞复制许可的初始开放结构 (IOS).
科学领域:
- 分子生物学
- 遗传学
- 生物化学
背景情况:
- 在真核生物中,DNA复制的启动对于细胞分裂至关重要.
- 微染色体维护 (MCM) 2-7 双六合体 (DH) 是启动DNA复制的关键复合体.
- MCM-DH溶解原始DNA的确切机制在很大程度上是未知的.
研究的目的:
- 阐明在复制启动过程中人类MCM-DH (hMCM-DH) 的初始DNA融化的结构机制.
- 了解hMCM-DH如何促进复制起源的初始开放结构 (IOS) 的形成.
- 调查IOS在授权DNA复制中的作用.
主要方法:
- 用冷电子显微镜 (cryo-EM) 确定与DNA结合的hMCM-DH的高分辨率结构.
- 生物化学测定以评估干扰IOS对DH形成和复制启动的影响.
- 基因组足迹绘制全基因组的hMCM-DH和IOS分布图.
主要成果:
- 对hMCM-DH的2.59-Å冷-EM结构揭示了一个狭窄的中央通道,它扭曲了结合的DNA.
- 通过在扭曲的DNA复合体内分离一个基对,hMCM-DH诱导初始开放结构 (IOS).
- IOS的干扰显著抑制了MCM- DH的形成和随后的复制启动.
- 基因组测绘显示IOS被聚集在发射区中, 与随机发射相关.
结论:
- hMCM-DH具有与初始链分离的DNA结合的内在机制,形成一个IOS.
- 这种IOS对于授权在人体细胞中启动DNA复制至关重要.
- 这些发现为了解如何选择和打开复制起源提供了结构基础.
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