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The shape of quadruple-helix DNA can be controlled

Not all DNA is in the double helix form described in textbooks since the 1950’s. Quadruple helix DNA, also known as G-quadruplex DNA, was identified in the human genome several decades ago, and extensively studied since then. Each cell in our body contains a copy of our DNA code made up of A, C, G and T, providing the blueprint for the organization and function of our bodies. Normally these letters combine in pairs to form the well-known double helix shape. However, some small lengths of DNA can exist as alternative shapes, which can affect how the instructions of the DNA code is ‘read’.

G-quadruplex DNA is a four-stranded structure made that can form a ‘knot’ in the DNA of living cells. In these structures, many Gs on the same stretch of DNA stick to each other instead of forming pairs between two strands. G-quadruplex DNA is known to be capable of forming many different types of structural shapes, yet little is understood about the factors controlling formation of these motifs.

However, since G-quadruplex DNA structures have been observed to play an important role in ‘reading’ of genes involved in development of human diseases, researchers expect that the variety of shapes they form will have an effect on when and how the DNA is read.

The findings of a study published this week in the journal Science Advances show how the sequence of DNA controls the formation of the variety of shapes in G-quadruplexes. Dr. Webba da Silva, from the School of Pharmacy and member of the Biomedical Sciences Research Institute at Ulster, and lead author of the study, says:

The ability to control G-quadruplex formation opens the pathway to exciting therapeutic, diagnostic and biotechnology applications for this molecule.

Using the information from biophysical studies, Webba da Silva’s lab was able to determine the most important parameters for controlling the folding of these architectures. ‘The problem is that the same aspect that makes these structures possible – repeated segments of multiple guanines – is what renders the final shape of these architectures so difficult to predict,’ says first author Dr. Scarlett Dvorkin. This study was part of her PhD work here at Ulster. The team included Dr Ioannis Karsisiotis, and was funded by the Biotechology and Biological Sciences Research Council (BBSRC) as well as a Vice-Chancellor Research Studentship.

The study demonstrates how to use the DNA sequence to programme the design of G-quadruplexes. The ability to make these architectures by design has been a sought after goal with impact in biomedicine, computer science, nano/optoelectronics, and biotechnology. Consequently, this work is certain to open up significant novel areas of inquiry.

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