Do you know: DNA motors have been found to shift gears
in 2025
????Scientists from Delft, Vienna, and Lausanne discovered that the protein machines that shape our DNA can change direction. Until now, researchers believed that the so-called SMC motors that make loops into DNA could only move in one direction. The discovery, which is published in cellcritical to understanding how these motors shape our genome and regulate our genes.
Linking DNA
“Sometimes, a cell needs to quickly switch which genes should be expressed and which genes should be turned off, for example in response to food, alcohol or heat. To turn genes on and off, cells use Structural Chromosome Maintenance (SMC) motors that act as switches to connect different segments of DNA,” explains first author Roman Barth. “However, SMC machines do not know which parts to connect. They simply load somewhere on the DNA and begin to shape it into a loop until they reach a point where they are forced to stop. That’s why they rely heavily on the ability to probe both sides of the DNA to find the right stop signals.”
Gearbox
Biophysicists at Delft University of Technology have now discovered that SMC motors can change direction, contrary to what was thought possible. “Our experiments show that SMCs pull DNA from one side at the moment, and then switch direction to pull DNA from the other side. By doing this, they can pull DNA into a loop from both sides over time. ???????We found that this was true for all types of SMC motors, of which there are many,” says Delft Professor Cees Dekker, who supervised the research. “You can compare it to a gearbox in a car: With a manual gearbox you can let the car move forward or reverse. We even identified the ‘gear lever’, a NIPBL protein subunit, in the protein integrin SMC motor.”
Impressive nanotechnology
To discover the rear gears of the SMC motor, the researchers used an advanced microscope to look at individual proteins on individual DNA molecules. That in itself is an amazing achievement, as Barth explains: “There are millions of proteins in one cell and the human body is made up of trillions of cells. It’s amazing to pull out a few proteins and be able to ‘see’ them one by one. a nanotechnology feat of nanometer-scale imaging — 100,000 smaller than the width of a human hair.”
Neurodegenerative diseases
“When we understand how SMC molecular motors shape DNA, we can start asking what goes wrong in diseases like cancer and neurogenerative diseases, and more importantly, how to correct it,” says Barth. “Gene dysregulation during the early stages of pregnancy can lead to neurogenerative diseases for example. In fact, there are a few serious diseases, such as Cornelia de Lange syndrome, which are linked to SMCs, where the motors probably fail to change right inside the embryo’s cells.”
Science in action
The study finally resolves the confusion in the scientific community about various conflicting theories about how SMCs work. Early research indicated that SMCs can move strictly in one direction only, while other research indicated that they pulled DNA in from both sides simultaneously. The discovery resolves these controversies. Barth: “Finding commonalities among SMC motors helps to focus and streamline the field of SMC research. We no longer need to look for a new mechanism for each type of SMC protein. It will accelerate the field towards applied science too. I would love to see this knowledge move into pharmaceutical companies, hospitals, and eventually doctors’ offices.”