Four-stranded DNA points to cancer cure

Cambridge University researchers say they’ve proved that four-stranded ‘quadruple helix’ DNA structures exist within the human genome.

Known as G-quadruplexes, they form in regions of DNA that are rich in the building block guanine, usually abbreviated to ‘G’. And, says the team, the discovery could make it possible in future to halt the runaway cell proliferation at the root of cancer.

There are clear links between concentrations of four-stranded quadruplexes and the process of DNA replication – crucial to cell division and production. Targeting quadruplexes with synthetic molecules that trap and contain these DNA structures could prevent cells from replicating their DNA and consequently block cell division.

“We are seeing links between trapping the quadruplexes with molecules and the ability to stop cells dividing, which is hugely exciting,” says Professor Shankar Balasubramanian.

“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.”

Scientists had already shown that quadruplex DNA can form in vitro, but this is the first time it’s been shown that they actually form in the DNA of human cells.The team 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.

Using fluorescence to mark the antibodies, the researchers could then identify ‘hot spots’ for the occurrence of four-stranded DNA – both where in the genome and, critically, at what stage of cell division.

While quadruplex DNA is found fairly consistently throughout the genome of human cells and their division cycles, the team found a big increase when the fluorescent staining grew more intense during the ‘s-phase’ – the point in a cell cycle where DNA replicates before the cell divides.

“The data supports the idea that certain cancer genes can be usefully interfered with by small molecules designed to bind specific DNA sequences,” said Balasubramanian.

“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.”