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Probe developed to view human quadruple-stranded DNA

18 January 2021
Appeared in BioNews 1079

A new method for visualising quadruple-stranded DNA within living cells has been developed, shedding light on its potential functions and interactions.

DNA, which normally exists in its famous double-stranded helix formation, was first observed in living cells in its four-stranded state, known as a G-quadruplex, last year (see BioNews 1057). However, these new probes reveal molecules that interact with G-quadruplexes inside living cells, potentially alluding to drug targets that disrupt their activity.

'Evidence has been mounting that G-quadruplexes play an important role in a wide variety of processes vital for life, and in a range of diseases, but the missing link has been imaging this structure directly in living cells' said Ben Lewis, who was lead author of the study. He also described the problem as 'like finding a needle in a haystack, but the needle is also made of hay'.

As G-quadruplexes are found in higher concentrations in cancer cells, they are thought to be involved in the progression of the disease, providing a potential target for novel cancer therapies.

To explore this, the researchers at Imperial College London developed a chemical probe called DAOTA-M2, which fluoresces when G-quadruplexes are present. Then, by analysing how the length of fluorescence, and therefore the amount of G-quadruplex, changes depending on the other molecules present, they could shed light on their potential roles and interactions within the cell.

Dr Marina Kuimova, one of the leads of the study, said that 'by applying this more sophisticated approach we can remove the difficulties which have prevented the development of reliable probes for this DNA structure.'

The researchers showed that G-quadruplexes interact with proteins called helicases, which are responsible for 'unwinding' DNA and beginning their breakdown. They also tested how other molecules interacted with G-quadruplexes, which may aid in the design of drugs for cancer treatment.

'Many researchers have been interested in the potential of G-quadruplex binding molecules as potential drugs for diseases such as cancers' said Professor Roman Vilar, who also co-led the study. 'Our method will help to progress our understanding of these potential new drugs.'

Rare four stranded DNA has been observed in action for the first time
Science Alert |  12 January 2021
Rare quadruple-helix DNA found in living human cells with glowing probes
Imperial College London |  8 January 2021
Scientists found a rare quadruple-helix DNA in living human cells
Tech Explorist |  8 January 2021
Visualising G-quadruplex DNA dynamics in live cells by fluorescence lifetime imaging microscopy
Nature Communications |  8 January 2021
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