Quadruple helix DNA discovery ‘key to fighting cancer’

For the first time, Cambridge scientists, including one of Indian origin, have discovered the four-stranded “quadruple helix” DNA in human cells which they say may be key to conquering cancer.

Researchers have proved that four-stranded ‘quadruple helix’ DNA structures — known as G—quadruplexes — also exist within the human genome and form in regions of DNA that are rich in the building block guanine ‘G’.

The study, published in Nature Chemistry shows 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.

“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 Cambridge’s Department of Chemistry.

“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,” Balasubramanian said in a statement.

Physical studies have shown that quadruplex DNA can form in vitro — in the ‘test tube’. Now, researchers 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.

Lead researcher Giulia Biffi generated antibody proteins that detect and bind to areas in a human genome rich in quadruplex-structured DNA, proving their existence in living human cells.

Researchers identified ‘hot spots’ for the occurrence of four-stranded DNA, using fluorescence to mark the antibodies.

A marked increase was shown when the fluorescent staining grew more intense during the ‘s-phase’ — the point in a cell cycle where DNA replicates before the cell divides.

Cancers are usually driven by genes called oncogenes that have mutated to increase DNA replication — causing cell proliferation to go out of control leading to tumour 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.

“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.

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