The double helix DNA structure is about as iconic as its gets. But geneticists have long speculated about the potential for a quadruple helix to exist — a four-stranded DNA structure. And indeed, computer models and lab experiments have suggested that it's theoretically possible.
Now, researchers working at Cambridge University have proven that quadruplexes do in fact exist in nature and they can be found right inside the cells of our bodies. Trouble is, their presence has been correlated with an increase in cellular replication — a process that could be contributing to the spread of some cancers.
Called the "G-quadruplex," it's a square-shaped structure that forms in regions of DNA that are rich in the building block, guanine (abbreviated as G, and is one of the four main nucleobases found in the nucleic acids DNA and RNA). It's held together by a special type of hydrogen bonding, one that forms a compact square matrix that can disrupt the DNA helix.
The researchers, a team that included Giulia Biffi, Shankar Balasubramanian and Julie Sharp, were able to isolate the quadruplexes within human cancer cells by using fluorescent biomarkers. The research was funded by Cancer Research UK.
Their discovery shows that a clear link can be established between the presence of concentrated amounts of quadruplexes and the process of DNA replication — a combo that's facilitating cell division and production. And indeed, the research showed that quadruplexes are more likely to occur in genes of cells that are rapidly dividing — including cancer cells. Moreover, they also tend to appear in the core of chromosomes and in telomeres (the caps on the tips of chromosomes that protect them from damage).
Consequently, the researchers are looking to further establish this potential link and create a cancer therapy in which synthetic molecules can be used to trap and contain these genetic trouble makers, thus preventing certain cells from replicating their DNA. The scientists are hoping that such a therapy could halt the runaway cell proliferation that's so characteristic of cancer. And indeed, when cancer cells divide rapidly, they often exhibit defects in their telomeres; subsequently, there may be a very intimate link between quadruplexes and tumorous growths.
To prove the existence of the quadruplexes, the researchers generated antibody proteins that could locate and bind to sections of the human genome that's rich in quadruplex-structured DNA. They used fluorescence to mark the antibodies, thus allowing them to visually see where the four-stranded DNA was doing its work within the genome — and at what stage of cell division.
Interestingly, the quadruplex DNA exists fairly consistently throughout the genome of human cells, but they increase dramatically during the ‘s-phase' of replication, the time when DNA replicates before the cell divides.
Tumors grow when cell proliferation spirals out of control — a process that's driven by genes called oncogenes that have mutated to increase DNA replication. As a result, the increased DNA replication rate in oncogenes leads to an increase in quadruplex structures. So, if the researchers can figure out a way to trap the quadruplex DNA with synthetic molecules, they could devise a novel way to treat cancer.
"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 Sharp through a release.
Read the entire study at Nature.
Images: Cambridge University.