Life’s blueprint TWISTS UNDER PRESSURE – a new discovery about DNA that rewrites what we know about genes

For decades, scientists assumed that when DNA got stuck during high-speed sequencing, it was tangled into knots. But a groundbreaking study from the University of Cambridge has revealed something far more elegant — and far more surprising. Those “knots” aren’t knots at all. They’re plectonemes, dynamic coils that form when DNA is twisted under pressure, like a telephone cord spiraling under tension. And this discovery doesn’t just change how we read DNA — it may rewrite our understanding of how genes turn on, how cells divide, and even how diseases take hold.

This isn’t just a quirk of laboratory experiments. Inside your body, DNA is constantly being pulled, copied, and twisted as cells grow and repair themselves. When that twisting goes wrong, it can disrupt how genes function, potentially leading to cancer, neurological disorders, or developmental defects. The new findings, published in Physical Review X, suggest that these coils — once dismissed as mere noise in data — could be critical players in the drama of life itself. If scientists can learn to read these twists like a language, they might unlock new ways to diagnose diseases, design drugs, or even edit genes with precision.

Key points:

• DNA’s “knots” aren’t always knots — many are plectonemes, spring-like coils formed when DNA twists under stress, a discovery that challenges decades of assumptions in genetic research.
• Nanopore sequencing, a revolutionary tool for reading DNA, may have been misinterpreting signals — what scientists thought were knots could be these coils, which behave differently and may influence gene activity.
• The coils form due to torque, a twisting force generated as DNA is pulled through nanopores — this same force may play a role in natural processes like DNA replication and transcription inside cells.
• Breaks in DNA strands (called “nicks”) reduce coil formation, proving that torsional stress is the driving force behind these structures—and suggesting a new way to detect DNA damage.
• The findings could transform nanopore technology, making it more accurate for sequencing, disease diagnosis, and even studying how genes are controlled in living organisms.
• Beyond the lab, this research hints at a deeper truth: DNA isn’t just a static code — it’s a dynamic, twistable molecule whose shape may be as important as its sequence.

The mystery of the missing knots

For years, scientists have used nanopores — microscopic holes in a membrane — to read DNA like a tickertape. As a strand of DNA threads through the pore, it disrupts an electrical current in a way that reveals its genetic letters: A, T, C, G. But sometimes, the current would hiccup in ways that didn’t match the expected sequence. The leading theory? The DNA had tied itself into a knot, jamming the pore like a shoelace caught in a door.

Ulrich Keyser, a physicist at Cambridge’s Cavendish Laboratory, wasn’t so sure. “Knots and plectonemes can look very similar in nanopore signals,” he explained. “But they come from very different physical mechanisms.” Knots are tight, tangled loops — think of a garden hose tied in a granny knot. Plectonemes, on the other hand, are more like a coiled telephone cord, formed when a strand twists around itself under tension. To test which was which, Keyser’s team designed an experiment that forced DNA to spin as it entered the nanopore, mimicking the twisting forces it might experience inside a cell.

What they found was stunning. The DNA didn’t just knot — it coiled, forming plectonemes up to 2,100 nanometers wide (about 1/50th the width of a human hair). When they increased the electrical voltage pulling the DNA through, the coils became even more pronounced. And when they introduced tiny breaks, or “nicks,” into the DNA strand — mimicking natural damage—the coils vanished. “When we controlled the molecule’s ability to rotate, we could change how often plectonemes appeared,” Keyser said. It was proof: these weren’t knots at all. They were dynamic structures, shaped by the same forces that twist DNA inside living cells.

Why a twisting DNA matters for your health

At first glance, this might seem like an abstract physics problem. But the implications ripple outward, touching some of the most fundamental questions in biology. Inside your cells, DNA isn’t just floating freely — it’s packed, looped, and twisted into complex shapes that help regulate which genes are turned on or off. When cells copy DNA (during replication) or transcribe it into RNA (to make proteins), the molecule gets pulled and twisted like a rubber band. If that twisting isn’t controlled, it can lead to errors — mutations that might trigger cancer, or misfires in gene expression that disrupt development.

Keyser suspects that plectonemes might be a natural way for cells to manage this stress. “I believe that the torsion in the molecules can actually give rise to the formation of other structures, like i-motifs and G-quadruplexes,” he said, referring to unusual DNA shapes that have been linked to gene regulation and disease. If plectonemes form during transcription or replication, they could act like molecular brakes, slowing down processes that might otherwise spin out of control.

The discovery also has practical implications for medicine. Nanopore sequencing is already used to diagnose genetic disorders, track infections, and even detect cancer from blood samples. But if plectonemes have been masquerading as knots, some of those readings might be inaccurate. “Just the fact that the DNA molecule can squeeze through the pore, where its stiffness is supposed to be much larger than the pore diameter, is quite amazing,” said Slaven Garaj, a physicist at the National University of Singapore who wasn’t involved in the study. By tuning the conditions in the nanopore — adjusting the salt concentration, the voltage, or the shape of the pore — scientists might be able to distinguish between true knots and these coils, making sequencing more precise.

Perhaps most intriguingly, the study hints at a new way to detect DNA damage. Since nicks in the DNA strand prevent plectonemes from forming, monitoring for these coils could become a tool for spotting breaks — early warnings of genetic instability that might lead to disease.

A deeper truth: DNA as a living, twisting code

Beyond the immediate applications, this research touches on a profound idea: DNA isn’t just a static string of letters. It’s a dynamic, twistable molecule whose shape is as critical as its sequence. For decades, scientists have focused on the genetic code — the A’s, T’s, C’s, and G’s — as the sole determinant of life’s instructions. But what if the way DNA twists and coils also carries information? What if the physical stresses on the molecule — whether from nanopores in a lab or enzymes in a cell — are part of the language of life itself?

This isn’t just speculation. Studies have shown that DNA’s 3D structure influences which genes are active. Loops and coils can bring distant genes into contact, turning them on or off like a dimmer switch. If plectonemes form naturally during these processes, they might be part of that regulatory system—a way for the cell to fine-tune its genetic symphony.

Keyser’s work suggests that we’ve only scratched the surface of this hidden layer of biology. “Our results indicate that this limitation could be overcome by resorting to nanopore-based setups,” he said, referring to the challenge of studying DNA’s twists in living cells. By refining nanopore technology, scientists might one day watch DNA coil and uncoil in real time, decoding not just the genetic text, but the physical poetry of how it’s read.

Sources include:

LiveScience.com

Journals.APS.org

Enoch, Brighteon.ai