DNA's double act: How genetic copies stick together during replication
Before a cell divides, its DNA is replicated so that each daughter cell inherits the same genetic information. The two copies, known as "sister chromatids," are held together by a ring-shaped protein complex called cohesin ...
Cohesin was first discovered nearly 30 years ago, but scientists have long pondered how the DNA-copying machinery manages to navigate genetic strands while encountering cohesin on its path.
Crick group leaders John Diffley and Frank Uhlmann, were both working on different aspects of DNA metabolism, until new experimental methods in their respective fields brought them together to answer this question, in two research papers published today in Cell and Molecular Cell.
"We hadn't worked with cohesin at all; we had been busy investigating the elements that make up the DNA copying machinery called the replisome," says Diffley. "Meanwhile, Uhlmann and his team were making huge progress in understanding how cohesin keeps DNA organized and aids cell division. And it was fortuitous timing that we were both ready to explore how cohesin and the replisome interact at the same time."
Cohesin throws its hat into the ring
As part of his Ph.D., sitting across both Uhlmann and Diffley's labs, Samson Glaser led the experiments to recreate cohesin and replisome interactions.
Cohesin is loaded onto the DNA double helix before replication (on the left). The replisome passes along the double helix, unzipping it and producing two identical sister copies. The team were keen to understand how the replication machinery navigates the cohesin ring, ensuring that both sister chromatids are entrapped after replication (on the right). Credit: Cell (2025). DOI: 10.1016/j.cell.2025.08.028
The researchers recorded the interaction of cohesin and the replisome over time, which allowed them to see the replisome (in the center) pass through the cohesin ring (green) as the DNA is replicated (white strands). Credit: Samson Glaser, Cell.
Experiments using 2D gel electrophoresis showed how cohesin often ends up embracing only one of the two DNA replication products. The darker band on the bottom right is cohesin around just one replication product. Credit: Masashi Minamino, Molecular Cell.