Discovery of four-stranded DNA gives hope for cancer breakthrough

Scientists at Cambridge University have proven the existence of four-stranded DNA in human cells for the first time, in what they say could be a major breakthrough in the fight against cancer

The discovery of the quadruple helix in the human genome comes 60 years after research at Cambridge by James Watson and Francis Crick first showed that DNA forms as a double helix.

A team led by Professor Shankar Balasubramanian and PhD student Giulia Biffi developed antibody proteins designed to bind to hotspots of quadruple helices that intertwine four, rather than two, DNA strands.

Using fluorescent biomarkers to highlight them, they were able to identify the areas where they occurred and also, critically, the time.

Levels of the four-stranded DNA – called G-quadruplexes because they are rich in guanine, one of four chemical bases that hold DNA together – peaked in the phase where cells replicate their DNA, just before dividing.

Mutated genes that increase DNA replication usually drive cancer, and the researchers concluded that G-quadruplexes are likely to be central to this process.

Previously, quadruple helices had been made synthetically but there was no evidence that they formed naturally until the new findings, published in the journal Nature Chemistry.

The team has already decreased the number of G-quadruplexes by using synthetic molecules to ‘fence’ them away and block DNA replication. However, their exact role in cell division remains unknown and translating the findings away from the laboratory is a long way off.

Professor Balasubramanian, of the university’s Department of Chemistry and the Cambridge Research Institute, said the “hugely exciting” research suggests G-quadruplexes “as targets for personalised treatments in the future.”

Dr Julie Sharp of Cancer Research UK, which funded the work, said: “The next part of this pipeline is to figure out how to target them in tumour cells.”