The molecular machines that loop chromosomes additionally twist DNA

Scientists from the Kavli Institute of Delft University of Technology and the IMP Vienna Biocenter have found a brand new property of the molecular motors that form our chromosomes. While six years in the past they discovered that these so-called SMC motor proteins make lengthy loops in our DNA, they’ve now found that these motors additionally put vital twists into the loops that they kind.

These findings assist us higher perceive the construction and performance of our chromosomes. They additionally present perception into how disruption of twisted DNA looping can have an effect on well being—as an example, in developmental ailments like “cohesinopathies.” The scientists printed their findings in Science Advances.

Imagine making an attempt to suit two meters of rope into an area a lot smaller than the tip of a needle—that is the problem each cell in your physique faces when packing its DNA into its tiny nucleus. To obtain this, nature employs ingenious methods, like twisting the DNA into coils of coils, so-called “supercoils” and wrapping it round particular proteins for compact storage.

Small DNA loops regulate chromosome capabilities

However, compaction is not sufficient. Cells additionally want to control the chromosome construction to allow its operate. For instance, when genetic data must be accessed, the DNA is regionally learn off. In specific, when it is time for a cell to divide, the DNA should first unpack, duplicate, after which correctly separate into two new cells.

Specialized protein machines referred to as SMC complexes (structural upkeep of chromosomes) play a vital position in these processes. Just a couple of years in the past, scientists at Delft and different locations found that these SMC proteins are molecular motors that make lengthy loops in our DNA, and that these loops are the important thing regulators of chromosome operate.

In the lab of Cees Dekker at TU Delft, postdocs Richard Janissen and Roman Bath now present clues that assist to crack this puzzle. They developed a brand new method to make use of “magnetic tweezers” by which they might watch particular person SMC proteins make looping steps in DNA.

Importantly, they had been additionally capable of resolve if the SMC protein would change the twist within the DNA. And strikingly, the workforce discovered that it did: the human SMC protein cohesin does certainly not solely pull DNA right into a loop, but additionally twists the DNA in a left-handed method by 0.6 turns in every step of making the loop.

A glimpse into the evolution of SMC proteins

What’s extra, the workforce discovered that this twisting motion is not distinctive to people. Similar SMC proteins in yeast behave the identical method. Remarkably, all the varied forms of SMC proteins from people and yeast add the identical quantity of twist—they flip DNA 0.6 instances at each DNA loop extrusion step. This reveals that the DNA extrusion and twisting mechanisms stayed the identical for very lengthy instances throughout evolution.

No matter whether or not DNA is looped in people, yeast, or every other cell—nature employs the identical technique.

These new findings will present important clues for resolving the molecular mechanism of this new sort of motor. Additionally, they clarify that DNA looping additionally impacts the supercoiling state of our chromosomes, which straight impacts processes like gene expression.

Finally, these SMC proteins are associated to numerous ailments resembling Cornelia de Lange Syndrome, and a greater understanding of those processes is important for monitoring down the molecular origins of those critical sicknesses.