DNA double helix structure (Billion Photos/Shutterstock)

THUWAL, Saudi Arabia — Scientists have finally captured footage of the microscopic machinery that allows our cells to copy DNA—a fundamental process necessary for life itself. Using a sophisticated imaging technique that freezes molecules in action, researchers watched as specialized proteins methodically unzipped the DNA double helix, revealing secrets about one of biology’s most essential processes.

The breakthrough comes from a team based at King Abdullah University of Science and Technology in Saudi Arabia. Their work, published in Nature, focuses on proteins called helicases, which act as molecular motors to separate the two strands of DNA before cell division.

The Unexpected Way DNA Gets Unwound

What’s surprising isn’t just that researchers saw the helicase working—it’s how it works. Scientists previously believed that ATP (adenosine triphosphate), the energy currency of cells, directly powered the DNA-unwinding process like fuel powers an engine. Instead, the researchers discovered that ATP acts more like a molecular spring or tension setter.

When ATP binds to the helicase, it creates tension within the protein structure. When that ATP is broken down, the tension releases, causing parts of the protein to rotate. This rotation pulls one DNA strand through the center of the ring-shaped helicase while pushing the other strand outward. This “ratcheting” mechanism moves the helicase along the DNA one notch at a time, progressively separating the strands.

The researchers nicknamed this unexpected mechanism an “entropy switch,” because it harnesses the natural tendency of molecules to move from ordered (high tension) to disordered (low tension) states.

To capture these molecular movements, the team used cryo-electron microscopy (cryo-EM), a technique that earned its developers the 2017 Nobel Prize in Chemistry. The method involves flash-freezing samples so quickly that water doesn’t form ice crystals, preserving the natural structure of biological molecules.

The team mapped 15 different conformational states of the helicase, creating what amounts to a molecular movie of DNA unwinding. This level of detail has never before been achieved for this fundamental biological process.

How DNA Replication Begins

Beyond simply watching helicases work, the researchers also discovered how DNA replication begins. When two helicase complexes assemble head-to-head at a specific DNA sequence called an origin, they melt the DNA at two symmetrically positioned sites. This creates bidirectional replication forks, allowing the cellular machinery to copy both directions of the genome simultaneously.

This head-to-head orientation explains why DNA replication is so efficient—cells can copy their entire genome in hours rather than days because multiple sections are copied simultaneously.

Why This Research Matters

Helicases are potential targets for anti-cancer drugs, as cancer cells depend heavily on DNA replication to support their rapid division. By understanding exactly how helicases function, researchers might develop new therapies that selectively interfere with cancer cells’ replication machinery.

The work also sheds light on viral replication. Many viruses, including the one that provided the helicase for this study, use similar mechanisms to reproduce inside infected cells. Better understanding these processes could lead to new antiviral strategies.

Perhaps most remarkably, the basic mechanism appears to be conserved across different organisms. The researchers compared their findings with known structures of replicative helicases from bacteria, archaea, and humans, finding striking similarities despite billions of years of evolutionary divergence.

This conservation highlights just how fundamental this mechanism is to life itself. It’s a reminder that despite the enormous diversity of living things, at the molecular level, we all rely on remarkably similar machinery to maintain and transmit our genetic information.

The scientists identified the exact protein building blocks (amino acids) that engage with the DNA during unwinding. They pinpointed specific amino acids that form critical contacts with the DNA bases and backbone.

By combining their observations across multiple experimental conditions, the researchers constructed a comprehensive model of the entire DNA unwinding cycle—from initial binding through ATP breakdown, DNA movement, and reset for the next cycle.

“From a design perspective, helicases exemplify energy-efficient mechanical systems. Engineered nanomachines using entropy switches could harness similar energy-efficient mechanisms to perform complex, force-driven tasks,” said study co-author Alfredo De Biasio, an assistant professor at the university.

Next time you consider the miracle of life—how a single cell can grow into a complex organism, or how your body constantly renews itself—remember that it all depends on these microscopic machines methodically unzipping DNA, one notch at a time, trillions of times throughout your body.