New discovery reveals twisting motion of molecular motors within the DNA

Scientists from the Kavli Institute of Delft College of Know-how and the IMP Vienna Biocenter found a brand new property of the molecular motors that form our chromosomes. Whereas six years in the past they discovered that these so-called SMC motor proteins make lengthy loops in our DNA, they now found that these motors additionally put important twists into the loops that they kind. These findings assist us higher perceive the construction and performance of our chromosomes. In addition they present perception into how disruption of twisted DNA looping can have an effect on health-;for example, in developmental illnesses like ‘cohesinopathies’. The scientists revealed their findings in Science Advances.

The wrestle of our cells

Think about attempting 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 attain this, nature employs ingenious methods, like twisting the DNA into coils of coils, so-called ‘supercoils’ (see photos for a visualisation) and wrapping it round particular proteins for compact storage.

Small DNA loops regulate chromosome capabilities

Nevertheless, compaction is not sufficient. Cells additionally want to manage the chromosome construction to allow its perform. For instance, when genetic data must be accessed, the DNA is regionally learn off. Specifically when it is time for a cell to divide, the DNA should first unpack, duplicate, after which correctly separate into two new cells. Specialised protein machines referred to as SMC complexes (Structural Upkeep of Chromosomes) play a important function in these processes. Just some 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 perform.

A brand new twist

Within the lab of Cees Dekker at TU Delft, postdocs Richard Janissen and Roman Tub now present clues that assist to crack this puzzle. They deloped a brand new method to make use of ‘magnetic tweezers’ by which they may watch particular person SMC proteins make looping steps in DNA. Importantly, they have been additionally in a position to resolve if the SMC protein would change the twist within the DNA. And strikingly, the staff discovered that it did: the human SMC protein cohesin does certainly not solely pull DNA right into a loop, but in addition 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 staff discovered that this twisting motion is not distinctive to people. Related SMC proteins in yeast behave the identical method. Strikingly, all the varied kinds of SMC proteins from human and yeast add the identical quantity of twist – they flip DNA 0.6 instances at each at each DNA loop extrusion step. This reveals that the DNA extrusion and twisting mechanisms stayed the identical for very lengthy instances throughout evolution. Regardless of whether or not DNA is looped in people, yeast, or some other cell – nature employs the identical technique.

Important clues

These new findings will present important clues for resolving the molecular mechanism of this new sort of motor. Moreover, they clarify that DNA looping additionally impacts the supercoiling state of our chromosomes, which instantly impacts processes like gene expression. Lastly, these SMC proteins are associated to varied illnesses equivalent to Cornelia de Lange Syndrome, and a greater understanding of those processes is important for monitoring down the molecular origins of those severe sicknesses.