The Quadruple Helix in the Human Genome Could Lead to New Cancer Drugs
The discovery of a quadruple helix in human cells could be a key to fighting cancer, according to the Cambridge researchers who made the findings. They come almost exactly 60 years after James Watson and Francis Crick burst in to the pub next to their Cambridge lab excitedly proclaiming that they had found the secret of life in the double helix structure of DNA.
Quadruple helixes intertwine four rather than two strands of DNA, and had been created in the lab by curious researchers, but it was generally thought that they didn’t exist in nature. But now these quadruple helixes – or G-quadruplexes – have been found in cancer cells, according to a study published in Nature Chemistry. The quadruple helix might be unique to human cancer cells – and the discovery means that cancer drugs to target these unusual DNA structures could be developed.
“We are seeing links between trapping the quadruplexes with molecules and the ability to stop cells dividing, which is hugely exciting,” said Professor Shankar Balasubramanian from the University of Cambridge’s Department of Chemistry and Cambridge Research Institute.
The research, which has been funded by Cancer Research UK, shows clear links between concentrations of four-stranded quadruplexes and the process of DNA replication, which is pivotal to cell division and production.
In 1953, Cambridge scientists James Watson and Francis Crick suggested what is now accepted as the first correct double-helix model of DNA structure in the journal Nature.
Their double-helix, molecular model of DNA was then based on a single X-ray diffraction image taken by Rosalind Franklin and Raymond Gosling in May 1952.
Cancers are usually driven by genes called oncogenes that have mutated to increase DNA replication – causing cell proliferation to spiral out of control, and leading to tumor growth.
The increased DNA replication rate in oncogenes leads to an intensity in the quadruplex structures. This means that potentially damaging cellular activity can be targeted with synthetic molecules or other forms of treatments.
“This research further highlights the potential for exploiting these unusual DNA structures to beat cancer – the next part of this pipeline is to figure out how to target them in tumor cells,” said Dr Julie Sharp, Senior Science Information Manager at Cancer Research UK.
Mr. Balasubramanian told the BBC, “I’m hoping now that the pharmaceutical companies will bring this on to their radar and we can perhaps take a more serious look at whether quadruplexes are indeed therapeutically viable targets. The quadruple helix DNA structure may well be the key to new ways of selectively inhibiting the proliferation of cancer cells. The confirmation of its existence in human cells is a real landmark.”
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