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Sensing changes in DNA structure implicated in disease

10 May 2021
Appeared in BioNews 1094

A 'chemical nose' can detect the quadruple-stranded DNA associated with diseases such as cancer.

Scientists at the University of California, Riverside and University of Parma, Italy have developed a sensing array to identify, differentiate and classify DNA secondary structures. Receptors similar to those found in the human nose, interact with a specific type of DNA fold and fluoresce, alerting the scientist to detect its presence in a biological sample. 

'If a DNA sequence is folded, it could prevent the transcription of a gene linked to that particular piece of DNA,' said co-senior author Professor Wenwan Zhong. 'In other words, this could have a positive effect by silencing a gene with the potential to cause cancer or promote tumours.' 

Conversely, DNA folding could also have a negative effect. 'DNA folds could potentially keep viral proteins from being produced to minimise immune response,' Professor Zhong added.

DNA is composed of four different nucleotides: guanine, cytosine, thymine, and adenine. Most of the time DNA is found in a double-stranded helix, resembling a ladder, but small regions can also fold into unusual structures. For example, guanine-rich stretches of DNA can fold to form a four-stranded G-quadruplex structure (see BioNews 1079). These structures are found more often in cancer cells, but not much is known about their role in disease. 

The research, published in Nature Chemistry, presents a non-invasive method that reliably detects the presence of G-quadruplexes and can differentiate between G-quadruplex structures and classify them into groups. 

The authors hope this rapid and simple method will help speed up research into the positive and negative functions of these DNA structures. They plan to build on their recent success by developing arrays to detect other DNA structures and tackling the complexities of RNA folding:

'RNA has even more complex structures than DNA, and is more difficult to analyse, but understanding its structure has great potential for disease research,' said Professor Zhong.

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