美国斯坦福大学Gheorghe Chistol课题组发现，单分子成像揭示后生动物中双向复制启动的机制。2024年6月11日，《细胞》杂志在线发表了这项成果。

通过实时观察GINS、Cdc45、TopBP1、RecQL4和DONSON的招募过程，研究人员发现复制的启动过程具有惊人的动态性。首先，TopBP1与源点瞬时结合，并在DNA合成开始前解离。其次，两个Cdc45被招募到一起，尽管Cdc45本身不能二聚。接着，两份DONSON和两份GINS同时到达源点，完成两个CMG螺旋的组装。最后，RecQL4被招募到CMG⋅DONSON⋅DONSON⋅CMG复合物中，并通过其ATP酶活性促进DONSON解离和CMG激活。

据介绍，后生动物基因组从数千个复制起源进行双向复制。复制启动需要在每个起源组装和激活两个CMG螺旋（Cdc45⋅Mcm2-7⋅GINS）。这需要几个复制启动因子（包括TopBP1、RecQL4和DONSON），它们的确切作用仍有争议。两个螺旋酶如何在每个源点正确组装和激活是一个长期存在的问题。

附：英文原文

Title: Single-molecule imaging reveals the mechanism of bidirectional replication initiation in metazoa

Author: Riki Terui, Scott E. Berger, Larissa A. Sambel, Dan Song, Gheorghe Chistol

Issue&Volume: 2024-06-11

Abstract: Metazoan genomes are copied bidirectionally from thousands of replication origins.Replication initiation entails the assembly and activation of two CMG helicases (Cdc45Mcm2-7GINS)at each origin. This requires several replication firing factors (including TopBP1,RecQL4, and DONSON) whose exact roles are still under debate. How two helicases arecorrectly assembled and activated at each origin is a long-standing question. By visualizingthe recruitment of GINS, Cdc45, TopBP1, RecQL4, and DONSON in real time, we uncoveredthat replication initiation is surprisingly dynamic. First, TopBP1 transiently bindsto the origin and dissociates before the start of DNA synthesis. Second, two Cdc45are recruited together, even though Cdc45 alone cannot dimerize. Next, two copiesof DONSON and two GINS simultaneously arrive at the origin, completing the assemblyof two CMG helicases. Finally, RecQL4 is recruited to the CMGDONSONDONSONCMG complexand promotes DONSON dissociation and CMG activation via its ATPase activity.

DOI: 10.1016/j.cell.2024.05.024

Source: https://www.cell.com/cell/abstract/S0092-8674(24)00533-6