The molecular machines that loop chromosomes also twist DNA

Scientists from the Kaveri Institute of TU Delft and the IMP Vienna Biocenter have discovered new properties of the molecular motors that shape chromosomes. Six years ago, they discovered that these so-called SMC motor proteins form long loops in our DNA, and now they have discovered that these motors also significantly twist the loops they form.

These findings help us better understand the structure and function of chromosomes. They also gain insights into how disruption of twisted DNA loops affects health, such as developmental diseases such as adhesions. scientists publish their findings scientific progress.

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

Small DNA loops regulate chromosome function

However, compression alone is not enough. Cells also need to regulate chromosome structure to achieve their functions. For example, when genetic information When access is required, the DNA is read locally. In particular, when a cell divides, the DNA must first be unpacked, replicated, and then properly separated into two new cells.

specialized protein A machine called the SMC complex (Structural Maintenance of Chromosomes) plays a key role in these processes. Just a few years ago, scientists in Delft and elsewhere discovered that these SMC proteins are molecular motors that form long loops in our DNA, and that these loops are key regulators of chromosome function.

In the laboratory of Cees Dekker at TU Delft, postdocs Richard Janissen and Roman Bath have now provided clues that may help solve this puzzle. They developed a new method using “magnetic tweezers” that allowed them to watch individual SMC proteins go through recycling steps in DNA.

Importantly, they were also able to determine whether SMC proteins alter the twisting of DNA. Surprisingly, the team found that this was indeed the case: the human SMC protein cohesin did not only pull the DNA into a loop, but also twisted the DNA 0.6 turns in a left-handed manner at each step in creating the loop.

A look at SMC protein evolution

What’s more, the team found that this twisting action isn’t unique to humans. Similar SMC proteins in yeast behave in the same way. Remarkably, all different types of SMC proteins from humans and yeast add the same amount of twist—they rotate the DNA by a factor of 0.6 on each ring Extrusion step. This suggests that DNA squeezing and twisting mechanisms have remained unchanged over long periods of time during evolution.

Whether DNA forms loops in humans, yeast, or any other cell, nature uses the same strategy.

These new findings will provide important clues to solve the molecular mechanism of this new type of motor. In addition, they also clearly pointed out that DNA looping will also affect the supercoiled state of chromosomes, directly affecting processes such as gene expression.

Finally, these SMC proteins have been implicated in a variety of diseases, such as Cornelia de Lange syndrome, and a better understanding of these processes is critical to tracking the molecular origins of these serious diseases.