'Dancing' DNA, imaged at the highest ever resolution, offers new genetic insight for the development of cancer therapies.
UK researchers have visualised circular DNA (minicircles) at an atomic scale for the first time. When the team induced a twist in the minicircles, they observed the DNA morph into diverse shapes, which attracted the binding of triplex-forming oligonucleotides (TFOs) – synthetic DNA sequences currently being trialled as anti-cancer agents.
'The videos we have developed enable us to observe DNA twisting in a level of detail that has never been seen before,' said first author Dr Alice Pyne from the University of Sheffield. 'Seeing is believing, but with something as small as DNA, seeing the helical structure of the entire DNA molecule was extremely challenging.'
The research team, who published their findings in Nature Communications, combined atomic force microscopy (a technique allowing nanoscale resolution) with supercomputer-powered modelling simulations to depict the double-stranded DNA complex in unprecedented detail.
'The laws of physics apply just as well to the tiny looped DNA as to sub-atomic particles and galaxies.' said Dr Sarah Harris from the University of Leeds, who led the research. 'We can use supercomputers to understand the physics of twisted DNA. This should help researchers such as Professor Zecheidrich design bespoke minicircles for future therapies.'
Professor Lynn Zechiedrich from Baylor College of Medicine in Houston, Texas, who provided the minicircles, said the images 'show, with remarkable detail, how wrinkled, bubbled, kinked, denatured, and strangely shaped they are, which we hope to be able to control someday.'
Understanding the relationship between DNA's structure and their TFO 'dancing partners', which can effectively suppress oncogenes, will hopefully aid the design of cancer therapeutics. Previous research from University College London also indicates that minicircles may themselves be viable as gene therapies, for conditions such as cystic fibrosis.