Dutch researchers reveal how a strand of DNA can fold

We finally know how long the DNA strands fold into the Mystic X. It was already known that the shape of chromosomes affects basic processes, such as cell division and turning genes on and off. We already knew that the cohesion protein complex plays a key role in folding chromosomes by holding together strands of DNA. But how cohesion ‘chooses’ which piece of DNA to bind to has been a big question.

Two Dutch studies have found answers: scientists from the TU Delft Register nature How tight the DNA helix is ​​determines how cohesion forms chromosomes. And at the Netherlands Cancer Institute, researchers have found the principle of the universal key lock that proteins use to bind cohesion to a piece of DNA. They post this Structural nature and molecular biology.

Our DNA is divided into several chromosomes, which are located in the cell nucleus in the form of long strands most of the time. But before a cell can divide, this chromosome must double. “These strings of spaghetti then turn into compact pieces of pasta,” says Benjamin Rowland, research group leader at NKI. With hands and feet he explains how DNA is doubled and coiled. The result is two identical chromosomes connected halfway: a mystical X of compressed DNA.

loops in DNA

A complex of several proteins, cohesin, plays an important role in this: it holds two strands of DNA together like a loop. The complex wraps the DNA so that it can regulate genes and holds two identical chromosomes together until the cell divides. Another protein, CTCF, determines where the cohesin loop binds to DNA.

“Our assumption was that CTCF simply acts as a stop signal for coherence, marking where in DNA it should create loops,” says Cees Dekker, professor of molecular biophysics at TU Delft. The process turned out to be more dynamic. Decker: “We discovered serendipitously that the amount of tension on a piece of DNA affects this blocking function of CTCF. If there is more force on the strand, CTCF stops the cohesion loop from forming. This ultimately has an effect on which genes are turned on and off.”

The tension is caused by protein machinery that moves over the DNA, for example, transcribing DNA into RNA. Roman Barth, lead author of the article, compared CTCF to a traffic light: “Pedestrians pay more attention when the road is busy. You don’t go red so fast. When many proteins in DNA are active, there is more stress and cohesin listens better for a signal.” CTCF Passage”.

Two building blocks

While Dekker’s group focused on the level of a single DNA molecule, Rowland’s group investigated the effect of cohesin on the chromosome scale. “In 2020, we revealed how CTCF relates to cohesiveness: according to the key-lock principle. Two CTCF building blocks fit perfectly into the cohesin quarry,” says Rowland. CTCF is not the only regulator of coherence. While CTCF binds cohesin to make DNA loops, another protein, SGO1, binds to cohesin to hold chromosomes together for cell division.

The researchers determined the spatial structure of SGO1. To their surprise, the protein turned out to have the same building blocks, and therefore also fit into the cohesin lock as a molecular key. Rowland: “This was a remarkable result. In fact, these two proteins seem to be just the tip of the iceberg of a universal mechanism by which cells build chromosomes.”

Scientists say neither study has direct applications. “It’s especially important to understand how cohesion works because it plays a critical role in chromosome structure in all organisms,” says Rowland.