Our genomes are massive and need to be well structured, to keep two sister strands of DNA together when cells divide, or to make sure certain genes are read at the correct time. 

A ring-shaped protein called cohesin is responsible for embracing two sister DNA strands, and also for creating loops within each strand. A popular theory for how cohesin forms these DNA loops is called ‘loop extrusion’. This idea is based on lab experiments where cohesin wraps around a strand of DNA and pulls the loop through the ‘ring’.

In research published this week in The EMBO Journal, the team, led by Thomas Guérin and Frank Uhlmann, tested this theory in live cells, by creating yeast with mutated cohesin that couldn’t extrude DNA loops.  

To their surprise, the DNA was still able to form loops. This resulted from two places on the same DNA being entrapped by a cohesin ring, in which the researchers call the ‘loop capture’ mechanism.

The former ‘loop extrusion’ model suggests that cohesin has some sort of motor activity in order to pull the strands through. But cohesin is a weak motor, and Thomas and Frank found that cohesin formed its loops near a DNA-reading machine called RNA polymerase, which is a much stronger motor. 

They propose that cohesin first catches a loop, then makes use of the strong motor action of RNA polymerase as it reads genes to be translated into proteins. This means that cohesin and RNA polymerase work together in order to translate the genome, as well as keep it in the right shape in the nucleus. 

Frank said: 

Cohesin is vital for survival and its properties haven’t changed much through evolution. Despite its importance, we still aren’t sure how it carries out its roles. It’s clear that cohesin can extrude loops in lab experiments, but the situation is very different inside a living cell. We’ve now shown that it captures two sections of DNA to make sure they are held together, and uses the DNA-reading machinery to make loops of the right size.

Thomas said: 

It was a really surprising moment when we saw that DNA strands could still form loops in yeast cells with loop-extrusion-deficient cohesin. This showed that there must be another mechanism taking place. A future challenge will be to understand how the loop capture mechanism might apply to a family of proteins that are similar to cohesin, which play other important roles in safeguarding our genomes.

Article by Clare Green from CrickNet 20.08.24