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Human quadruple-stranded DNA discovered

27 July 2020
Appeared in BioNews 1057

Quadruple-stranded DNA has been observed in healthy human cells for the first time, shedding light on its possible role in cancer.

Scientists based at the universities of Cambridge and Leeds, and Imperial College London, are now able to visualise and track this structure, formed from four separate DNA strands, in living cells. This will allow them to investigate its function and role within its natural environment.

'This forces us to rethink the biology of DNA' said Imperial's Dr Marco Di Antonio, who co-lead of the project. 'It is a new area of fundamental biology, and could open up new avenues in diagnosis and therapy of diseases like cancer.'

DNA, which is normally held in a two-stranded double helix structure, has been observed in its quadruple-stranded form before. However, this required either killing the cells, or using large volumes of chemical probes which would interact with the structures themselves.

Using a technique called single-molecule microscopy, the researchers were able to use much smaller amounts of fluorescent markers to identify the structures. This allowed the markers to bind very quickly with the DNA without altering its shape, enabling its formation and activity to be tracked and analysed.

The researchers have suggested that quadruple-stranded DNA arises in order to temporarily hold the double helix open, allowing it to be expressed and for proteins to be produced – making it a type of temporary epigenetic modification. These structures were found to be far more common in cancer cells than in healthy tissue and are normally associated with genes with established roles in cancer.

With greater knowledge of the role played by quadruple-stranded DNA, Dr Di Antonio hopes that this research will pave the way for further work into possible cancer treatments:

'We know [quadruple-stranded DNA] appears to be more prevalent in cancer cells', he said, 'and now we can probe what role it is playing and potentially how to block it, potentially devising new therapies.'

The research was published in Nature Chemistry

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