Four-stranded DNA has been seen before in some cancer cells and in lab-based chemistry experiments, but this is the first time the molecule has been visualised in healthy, living human cells, as a stable structure created by normal cellular processes.
"We've undoubtedly demonstrated that the quadruple-strand DNA forms in living cells," says Marco Di Antonio at Imperial College London. "This forces us to rethink the biology of DNA."
The DNA molecule is made up of four nucleobases - adenine, cytosine, guanine and thymine - and can configure itself in a number of ways. It creates a four-stranded structure when four guanine bases form a square - guanine is the only base able to bond with itself.
Di Antonio, who conducted the work while at the University of Cambridge, and his colleagues were able to visualise the quadruple form within human tissue by attaching a new kind of fluorescent marker to DNA in living cells. He says the discovery may improve our understanding of how the genetic material divulges its information.
"We know exactly what DNA does," says Di Antonio, "but how does the cell know where to express genes and how much protein to make?" The researchers speculate that the quadruplex structure forms to hold the molecule open and facilitate the reading of the genetic code and thus the production of proteins. It may also influence the amount of each protein that is made.
Usually, this function is performed by epigenetic markers - chemical tags on DNA that increase or decrease the activity of genes - and it seems that the quadruplex form of DNA has a similar role. "There is a sort of crosstalk between the formation of quadruplex DNA and epigenetic markers," says Di Antonio. "The quadruplex form is an epigenetic mark in its own right."
Zoรซ Waller at the University of East Anglia, UK, says the work adds to the evidence that the quadruplex structures form part of normal DNA regulation and function, and that our view of the DNA double helix may be out of date. "We presume that this is the normal, native state of DNA, but this work is another exceptional example of mounting evidence that DNA is not a fixed structure or shape," she says.
Journal reference: Nature Chemistry, DOI: 10.1038/s41557-020-0506-4
1. Where did they even find a quad-helix sample of DNA? Did they make it themselves? Or is there some special sample they have on file in a vault somewhere that people sign out when they want to poke at it? Where did it come from? Did some lab tech hold up a random sample and blink in surprise?
2. Is this a new discovery or have quad-helix DNA been around and known about for decades?
3. What does this mean in terms of data density of DNA? Can you store even more copies of the Library of Congress in a drop of water now?
4. What kinds of people exhibit this genetic feature? How common is it? Do they eat avocados?
If you go to the source document, we get the following:
"Substantial evidence now exists to support that formation of DNA G-quadruplexes (G4s) is coupled to altered gene expression. However, approaches that allow us to probe G4s in living cells without perturbing their folding dynamics are required to understand their biological roles in greater detail. Herein, we report a G4-specific fluorescent probe (SiR-PyPDS) that enables single-molecule and real-time detection of individual G4 structures in living cells. Live-cell single-molecule fluorescence imaging of G4s was carried out under conditions that use low concentrations of SiR-PyPDS (20 nM) to provide informative measurements representative of the population of G4s in living cells, without globally perturbing G4 formation and dynamics. Single-molecule fluorescence imaging and time-dependent chemical trapping of unfolded G4s in living cells reveal that G4s fluctuate between folded and unfolded states. We also demonstrate that G4 formation in live cells is cell-cycle-dependent and disrupted by chemical inhibition of transcription and replication. Our observations provide robust evidence in support of dynamic G4 formation in living cells."
The science reporter's job is to turn that into something which makes sense to regular people.