When DNA forms, it usually creates the characteristic double-helix that we’ve all come to recognize. However, given the right ingredients, DNA can fold with another pair of strands to create a quadruple-stranded structure that may have some pretty important roles. These structures, called G-quadruplexes (G4), have only been seen in chemistry lab experiments or in some cancer cells, so understanding exactly what their roles are has been difficult, until now.
Scientists have now produced the first visualization of a G-quadruplex formation in live, healthy cells. By developing a fluorescent marker that can bind to G4s, the researchers could track the formation of a quadruplex structure for the first time, with the results published in Nature. This provides confirmation that normal cellular processes produce these structures, and not a process gone haywire like those in cancer.
“For the first time, we have been able to prove the quadruple helix DNA exists in our cells as a stable structure created by normal cellular processes. This forces us to rethink the biology of DNA. It is a new area of fundamental biology, and could open up new avenues in diagnosis and therapy of diseases like cancer,” said one of the lead researchers Dr Marco Di Antonio in a statement.
DNA is made of four nucleotide bases: adenine, guanine, cytosine, and thymine. A G-quadruplex forms when four guanines, the only base that can bond with itself, join together to create a stacked but stable structure. This four-stranded complex is mostly found at the end of chromosomes and in regulatory regions, and may be involved in expression of various genes across the human genome.
G4s remain fairly enigmatic in their role. The authors of this study believe G4s temporarily hold the DNA strands apart so that proteins can read the nucleotide code and produce proteins. They also appear to interact with genes implicated in cancer, such as oncogenes, and are found at much higher rates in cancerous cells, but any causal links between G4s and cancer have never been established.
Whilst this is a massive breakthrough in genetics, we have been aware of G-quadruplexes for many years. However, traditionally the technique to track them may have damaged the DNA and actually led to the production of more G4s than what was originally present, and so separating those that were generated naturally from those produced by testing has been a challenge.
These results were instead made possible by a new technique to visualize the G4s in living cells and track their formation. A fluorescent marker was added that would attach to individual G4s, before the team used microscopy to track the bright marker – and with it, the role they play in the DNA.
“Now we can track G4s in real time in cells we can ask directly what their biological role is,” said Dr Di Antonio.
With this new probing technique, it’s very possible that scientists could soon fully illuminate the role of these perplexing structures within our genes, and begin to understand just how important they are.