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Supercoiled DNA is far more dynamic than the “Watson-Crick” double helix

15 October 2015

Researchers have imaged in unprecedented detail the three-dimensional structure of supercoiled DNA, revealing that its shape is much more dynamic than the well-known double helix.

Various DNA shapes, including figure-8s, were imaged using a powerful microscopy technique by researchers at the Baylor College of Medicine in the US, and then examined using supercomputer simulations run at the University of Leeds.

As reported online in the journal Nature Communications, the simulations also show the dynamic nature of DNA, which constantly wiggles and morphs into different shapes – a far cry from the commonly held idea of a rigid and static double helix structure. Dr Sarah Harris from the School of Physics and Astronomy led the computer simulation research side of the study and explained that this is because the action of drug molecules relies on them recognising a specific molecular shape – much like a key fits a particular lock.

The double helix shape has a firm place in the public's collective consciousness. It is referenced in popular culture and often features in art and design. But the shape of DNA isn’t always that simple.
Dr Harris said, “When Watson and Crick described the DNA double helix, they were looking at a tiny part of a real genome, only about one turn of the double helix. This is about 12 DNA ‘base pairs’, which are the building blocks of DNA that form the rungs of the helical ladder.

“Our study looks at DNA on a somewhat grander scale – several hundreds of base pairs – and even this relatively modest increase in size reveals a whole new richness in the behaviour of the DNA molecule.”

There are actually about 3 billion base pairs that make up the complete set of DNA instructions in humans. This is about a metre of DNA. This enormous string of molecular information has to be precisely organised by coiling it up tightly so that it can be squeezed into the nucleus of cells.
To study the structure of DNA when it is crammed into cells, the researchers needed to replicate this coiling of DNA.

Improving our understanding of what DNA looks like when it is in the cell will help us to design better medicines, such as new antibiotics or more effective cancer chemotherapies.

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