Structure of DNA rewritten as scientists find genetic ‘towers’ in human cells

A team of researchers from the University of Cambridge, Imperial College London and Leeds University invented a fluorescent marker that can attach to a quadruple helix, allowing it to be seen for the first time so experts can begin discovering what role it plays in cells.

Lead researcher Dr Marco Di Antonio, of Imperial College London, said: “For the first time, we have been able to prove the quadruple helix DNA exists in our cells as a stable structure created by normal cellular processes. 

“This forces us to rethink the biology of DNA. It is a new area of fundamental biology, and could open up new avenues in diagnosis and therapy of diseases like cancer.

“Now we can track G4s in real time in cells, we can ask directly what their biological role is. We know it appears to be more prevalent in cancer cells, and now we can probe what role it is playing and potentially how to block it, potentially devising new therapies.”

Scientists have been able to produce quadruple helix DNA in the lab before now, but it was unknown whether it could ever occur in living cells or what it would do if found there.

The team believes G4s form in DNA in order to temporarily hold it open and facilitate processes like transcription, where the DNA instructions are read and proteins made. This is a form of “gene expression”, where part of the genetic code in the DNA is activated.

The new DNA is found more often in genes involved in cancer, and is detected in larger numbers within cancer cells. 

The scientists are now planning to track the role of quadruple helix in specific genes to see whether they can find if it is influencing cancer development. If so, it could help stop cancer when it is first developing. 

Quadruple DNA has been tricky to see in cells up to now because the chemical probes that allow it to be seen under a microscope can disrupt the genetic material, changing its structure.

But Dr Aleks Ponjavic, of the University of Leeds, helped develop a new marker which kept the structure intact.

He said: “Scientists need special probes to see molecules within living cells – however, these probes can sometimes interact with the object we are trying to see. 

“By using single-molecule microscopy, we can observe probes at 1000-fold lower concentrations than previously used. In this case, our probe binds for just milliseconds without affecting its stability, which allows us to study the behaviour in their natural environment without external influence.”

The scientists found that the quadruple helix DNA forms and dissipates very quickly, suggesting they are there to perform a certain function swiftly and may be damaging to the normal cell process if they last too long.

The research was published in the journal Nature Chemistry.

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