Scientists have found that the protein machines involved in shaping our DNA are capable of switching directions. Previously, it was thought that these SMC motors, which create loops in DNA, could only operate in a single direction. This discovery is vital for understanding how these motors influence our genome and control gene expression.
A team of scientists from Delft, Vienna, and Lausanne has revealed that the protein machines responsible for forming our DNA can indeed alternate their direction. Up until now, researchers believed that these SMC motors that form loops in DNA were limited to moving in one specific way. This groundbreaking finding, published in Cell, is crucial for gaining insights into how these motors organize our genome and manage gene regulation.
Connecting DNA
“At times, cells need to quickly adjust which genes to express or silence, as seen in response to factors like food, alcohol, or temperature changes. To turn genes off and on, cells deploy Structural Maintenance of Chromosomes (SMC) motors, which function like switches connecting various segments of DNA,” explains lead author Roman Barth. “However, SMC motors don’t inherently know which segments to connect. They start attaching somewhere on the DNA and shape it into a loop until they encounter a point that prevents further movement. Therefore, they depend on the ability to explore both sides of the DNA to locate the appropriate stop signals.”
Gearbox
Researchers at Delft University of Technology have now discovered that SMC motors are capable of changing direction, which was previously thought to be impossible. “Our experiments demonstrate that SMCs can pull DNA from one side and then switch to pull from the opposite side. This allows them to gradually form loops by pulling DNA from both sides,” says Delft professor Cees Dekker, who oversaw the study. “This mechanism can be likened to a car’s gearbox: with a manual transmission, you can move the car forwards or backwards. We even identified a ‘gear lever,’ the protein subunit NIPBL, in the cohesin SMC motor protein.”
Impressive nanotechnology
To reveal the reverse capability of SMC motors, the research team utilized a sophisticated, custom-built microscope to observe single proteins on individual DNA strands. This achievement is significant, as Barth points out: “A single cell is filled with millions of proteins, and the human body comprises trillions of cells. Isolating a few proteins to observe them individually is an extraordinary feat of nanotechnology, allowing imaging at a scale of nanometers—100,000 times smaller than the width of a human hair.”
Neurodegenerative diseases
“Understanding how SMC molecular motors shape DNA could lead us to explore what goes wrong in conditions such as cancer and neurodegenerative diseases, and how we might correct these issues,” Barth notes. “Neurodegenerative diseases can arise from improperly regulated genes during early pregnancy. Indeed, some severe disorders, like Cornelia de Lange syndrome, are associated with SMCs, suggesting that these motors might not function correctly in the embryonic cells.”
Science in action
This study clarifies existing confusion within the scientific community regarding conflicting theories about SMC functions. Initial studies proposed that SMCs moved strictly in one direction, while others suggested they pulled DNA in from both sides at the same time. This new discovery addresses those discrepancies. Barth adds, “Finding common characteristics among SMC motors enables researchers to streamline their studies. We no longer need to search for a unique mechanism for each type of SMC protein. This advancement will also help propel the field towards practical applications. I hope this knowledge transitions into pharmaceutical companies, hospitals, and ultimately, doctors’ offices.”
