'Quadruple Helix' DNA Discovered In Human Cells

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In 1953, Cambridge researchers Watson and Crick published a paper describing the interweaving 'double helix' DNA structure - the chemical code for all life. Now, in the year of that scientific landmark's 60th Anniversary, Cambridge researchers have published a paper proving that four-stranded 'quadruple helix' DNA structures - known as G-quadruplexes - also exist within the human genome. They form in regions of DNA that are rich in the building block guanine, usually abbreviated to 'G'.

The findings mark the culmination of over 10 years investigation by scientists to show these complex structures in vivo - in living human cells - working from the hypothetical, through computational modelling to synthetic lab experiments and finally the identification in human cancer cells using fluorescent biomarkers. 

The research, published today in Nature Chemistry and funded by Cancer Research UK, goes on to show clear links between concentrations of four-stranded quadruplexes and the process of DNA replication, which is pivotal to cell division and production. 

By targeting quadruplexes with synthetic molecules that trap and contain these DNA structures - preventing cells from replicating their DNA and consequently blocking cell division - scientists believe it may be possible to halt the runaway cell proliferation at the root of cancer. 

"The research indicates that quadruplexes are more likely to occur in genes of cells that are rapidly dividing, such as cancer cells. For us, it strongly supports a new paradigm to be investigated - using these four-stranded structures as targets for personalised treatments in the future."

Physical studies over the last couple of decades had shown that quadruplex DNA can form in vitro - in the 'test tube', but the structure was considered to be a curiosity rather than a feature found in nature. The researchers now know for the first time that they actually form in the DNA of human cells. 

"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 tumour cells," said Dr Julie Sharp, senior science information manager at Cancer Research UK. 

"We have found that by trapping the quadruplex DNA with synthetic molecules we can sequester and stabilise them, providing important insights into how we might grind cell division to a halt," said Balasubramanian. 

The study showed that if an inhibitor is used to block DNA replication, quadruplex levels go down - proving the idea that DNA is dynamic, with structures constantly being formed and unformed. 

The researchers also previously found that an overactive gene with higher levels of Quadruplex DNA is more vulnerable to external interference. 

"The possibility that particular cancer cells harbouring genes with these motifs can now be targeted, and appear to be more vulnerable to interference than normal cells, is a thrilling prospect. 

Via: "Phys"