KAUST researchers capture DNA unwinding at the atomic scale.

Jeddah, March 26, 2025, A groundbreaking study from King Abdullah University of Science and Technology (KAUST), published in Nature, has captured the precise moment DNA begins to unwind, marking the initial step in DNA replication. This discovery provides crucial insights into the fundamental processes that enable cells to duplicate their genetic material, essential for growth and reproduction.

According to a KAUST press release, the research team, led by Assistant Professor Alfredo De Biasio and Professor Samir Hamdan, utilized cryo-electron microscopy (cryo-EM) and deep learning techniques to observe how the helicase enzyme Simian Virus 40 Large Tumor Antigen interacts with DNA. Their findings offer the most detailed description of the first steps of DNA replication, identifying 15 atomic states that illustrate how helicases initiate the unwinding process.

“The achievement is not only a milestone in helicase research but also in observing enzyme dynamics at atomic resolution,” the release stated.

Helicases bind to DNA, breaking the chemical bonds that hold the double helix together and pulling the strands apart, allowing replication to proceed. Without this crucial step, DNA replication cannot occur. In essence, helicases function as molecular machines—or nanomachines due to their microscopic scale.

The study revealed that as adenosine triphosphate (ATP) is consumed, it reduces physical constraints, enabling helicases to move along DNA and progressively unwind the strands. ATP consumption acts as a molecular switch that increases entropy in the system, facilitating helicase movement.

De Biasio explained, “The helicase doesn’t pry DNA apart in one motion but cycles through conformational changes that gradually destabilize and separate the strands.”

Among the key discoveries was that two helicases initiate DNA unwinding at separate sites simultaneously, allowing for a bidirectional unwinding mechanism with unique energy efficiency. Since helicases move along a single strand in one direction, this coordination enables the process to occur efficiently in both directions.

This efficiency, emphasized De Biasio, not only advances the fundamental understanding of DNA replication but also positions helicases as models for new nanotechnology designs.

“From an engineering perspective, helicases exemplify energy-efficient mechanical systems. By harnessing entropy switches, engineered nanomachines could replicate these mechanisms to perform complex, force-driven tasks,” he said.