Alice and Kavit alongside collaborators have published a paper in Nature Commmunications this week, ‘Base-pair resolution analysis of the effect of supercoiling on DNA flexibility and major groove recognition by triplex-forming oligonucleotides’.
Videos accompanying the paper, derived from high resolution AFM images of DNA and molecular dynamics (MD) simulations, show for the first time how small circles of DNA adopt dance-like movements.
The footage is based on the highest resolution images of a single molecule of DNA ever captured. They show in unprecedented detail how the stresses and strains that are placed on DNA when it is crammed inside cells can change its shape.
Previously scientists were only able to see DNA by using microscopes that are limited to taking static images. But now the Yorkshire team has combined advanced atomic force microscopy with supercomputer simulations to create videos of twisted molecules of DNA.
Alice said:
“Seeing is believing, but with something as small as DNA, seeing the helical structure of the entire DNA molecule was extremely challenging.
The videos we have developed enable us to observe DNA twisting in a level of detail that has never been seen before.”
The images are so detailed it is possible to see the iconic double helical structure of DNA, but when combined with the simulations, the researchers were able to see the position of every single atom in the DNA and how it twists and writhes.
Every human cell contains two metres of DNA. In order for this DNA to fit inside our cells, it has evolved to twist, turn and coil. That means that loopy DNA is everywhere in the genome, forming twisted structures which show more dynamic behaviour than their relaxed counterparts.
The team looked at DNA minicircles, which are special because the molecule is joined at both ends to form a loop. This loop enabled the researchers to give the DNA minicircles an extra added twist, making the DNA dance more vigorously.
When the researchers imaged relaxed DNA, without any twists, they saw that it did very little. However, when they gave the DNA an added twist, it suddenly became far more dynamic and could be seen to adopt some very exotic shapes. These exotic dance-moves were found to be the key to finding binding partners for the DNA, as when they adopt a wider range of shapes, then a greater variety of other molecules find it attractive.
Previous research from Stanford, which detected DNA minicircles in cells, suggests they are potential indicators of health and ageing and may act as early markers for disease.
As the DNA minicircles can twist and bend, they can also become very compact. Being able to study DNA in such detail could accelerate the development of new gene therapies by utilising how twisted and compacted DNA circles can squeeze their way into cells.
One of our collaborators who produces the minicircles used in this study said:
“Dr. Pyne and her co-worker’s new AFM structures of our supercoiled minicircles are extremely exciting because they show, with remarkable detail, how wrinkled, bubbled, kinked, denatured, and strangely shaped they are which we hope to be able to control someday.”
You can read the paper here: