The molecular machines that loop the chromosomes also twist the DNA

Scientists from the Kavli Institute of the Delft University of Technology and the IMP Vienna Biocenter have discovered a new property of the molecular motors that form our chromosomes. While six years ago they knew that this so-called SMC motor protein makes long loops in our DNA, they now know that these motors also put more twists on the loops they form. .

These findings help us better understand the structure and function of our chromosomes. They also provide insight into how disruption of twisted DNA looping affects health—for example, in developmental disorders such as “cohesinopathies.” The scientists PUBLISHED their findings on Advances in Science.

Imagine trying to fit two meters of string into a space smaller than the tip of a needle—that’s the challenge every cell in your body faces when packing its DNA into its tiny nucleus. To achieve this, nature uses clever strategies, such as twisting DNA into coils of coils, called “supercoils” and wrapping them in special proteins for compact storage.

Small loops of DNA regulate the functions of chromosomes

However, compaction is not enough. Cells must also regulate the structure of chromosomes to enable their movement. For example, when genetic information should be accessible, DNA is read locally. In particular, when it’s time for a cell to divide, the DNA must first be unpacked, duplicated, and then properly separated into two new cells.

SPECIALISTS protein Machines called SMC complexes (structural maintenance of chromosomes) play an important role in these processes. Just a few years ago, scientists in Delft and elsewhere discovered that these SMC proteins are molecular motors that create long loops in our DNA, and that these loops are the main ones. regulator of chromosome function.

In Cees Dekker’s lab at TU Delft, postdocs Richard Janissen and Roman Bath are now providing clues that will help crack this puzzle. They developed a new method of using “magnetic tweezers” where they can look at individual proteins in the SMC that take steps to loop the DNA.

Importantly, they were also able to resolve whether the SMC protein changes the DNA twist. And surprisingly, the team found that it did: the human SMC protein cohesin actually not only pulls the DNA into a loop, but also spins the DNA in a left-handed fashion by 0.6 turns at each step in the creation of the loop.

An overview of the evolution of SMC proteins

Furthermore, the team found that this distorted action is not unique to humans. The same SMC proteins in yeast behave in a similar way. Remarkably, all the different types of SMC proteins from humans and yeast add the same amount of twist—it repeats DNA 0.6 times per DNA. loop extrusion step. This shows that DNA extrusion and twisting mechanisms have remained the same for a long time during evolution.

It doesn’t matter if the DNA is looped in humans, yeast, or any other cells—nature uses the same strategy.

These new findings will provide important clues for unraveling the molecular mechanism of this new type of motor. In addition, they explained that DNA looping also affects the supercoiling state of our chromosomes, which directly affects processes such as gene expression.

Finally, these SMC proteins are associated with various diseases such as Cornelia de Lange Syndrome, and a better understanding of these processes is important for tracing the molecular origin of these serious diseases.