弗朗西斯·克里克研究所Frank Uhlmann小组宣布他们揭示了复制体通过内聚环。相关论文发表在2025年9月16日出版的《细胞》杂志上。

该课题组研究人员的主题是生化重建和单分子荧光显微镜，以直接可视化复制体-内聚蛋白相遇。该课题组研究人员发现易位的真核生物复制性Cdc45-Mcm2-7-GINS （CMG）解旋酶与其他类似大小的障碍不同，它很容易通过内聚环。完全重组的复制体也通过内聚环，使两个复制产物都被困在里面。复制体的传代主要由DNA聚合酶α和ε辅助，这一发现需要重新评估典型内聚建立因子的作用。他们的发现证明存在一种简单的机制，将基因组复制与染色体分离联系起来：复制体通过内聚环传递。

据悉，在真核生物基因组复制之后，环状内聚蛋白复合体包围了两个新合成的姐妹染色单体，使它们在细胞分裂期间能够忠实地分离。复制体通过内聚环被设想为一种确保复制产物共捕获的故障安全机制——复制体是否确实可以通过内聚环仍然未知。

附：英文原文

Title: Replisome passage through the cohesin ring

Author: Samson Glaser, Maxim I. Molodtsov, John F.X. Diffley, Frank Uhlmann

Issue&Volume: 2025-09-16

Abstract: Following eukaryotic genome replication, the ring-shaped cohesin complex embraces the two newly synthesized sister chromatids, enabling their faithful segregation during cell divisions. Replisome passage through cohesin rings has been envisioned as a fail-safe mechanism that ensures co-entrapment of replication products—whether replisomes can indeed pass through cohesin rings remains unknown. Here, we use biochemical reconstitution and single-molecule fluorescence microscopy to directly visualize replisome-cohesin encounters. We find that the translocating eukaryotic replicative Cdc45-Mcm2-7-GINS (CMG) helicase, unlike other obstacles of similar size, readily passes through cohesin rings. Fully reconstituted replisomes also pass cohesin rings to leave both replication products trapped inside. Replisome passage is primarily aided by DNA polymerases α and ε, a finding that necessitates re-evaluation of canonical cohesion establishment factor roles. Our findings demonstrate the existence of a simple mechanism that links genome replication with chromosome segregation: replisome passage through cohesin rings.

DOI: 10.1016/j.cell.2025.08.028

Source: https://www.cell.com/cell/abstract/S0092-8674(25)01017-7