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I-Motif DNA, Interview to the Professor that made the discovery - Relationship with Telomeres

Scientists have discovered a new kind of DNA inside humans. The new DNA, known as the i-motif, visually differs from the well-known structure of DNA due to its twisted knot. Online magazine Sputnik discussed the topic with Professor Marcel Dinger, a molecular biologist at the Garvan Institute of Medical Research, who co-led the study.

Sputnik: Can you tell us about where this DNA is located and how it's different from what we are used to, the double helix? Marcel Dinger: The new DNA is still part of our chromosomes, it's still part of our genome just like all our double helical DNA, what we've really found is that parts of our genome, parts of our chromosomes can fold in this different way, that's different to the double helix, into this so-called i-motif. Which is like a four-stranded knot, you have to really see a picture of it to appreciate it, but it's an entirely different structure which does not bond in the normal double helix shape and instead forms a different shape which forms the so-called i-motif.

Sputnik: Is this something that all humans have? Is this in all cells or is it just in some people, in some cells?

Marcel Dinger: We believe that this structure will form in all cells and it's a normal and natural part of the genome, both the human genome and probably also the genomes of all organisms on Earth, and is actually just a part of what DNA can do in normal physiological conditions, and this is really what the surprise was here, because it had initially been thought that this particular structure could only be created in artificial conditions, in the outside laboratory. The interesting thing here was that the cells in normal physiological conditions can also produce this particular shape. We actually expect that there are probably tens of thousands of these structures across the human genome.

Sputnik: Can you tell us what the significance is of understanding now that this is in living cells and part of the human DNA?

Marcel Dinger: The fact that this is a part of biology, normal biology is a really important finding, because it means that nature probably has had for millions and millions of years the opportunity to exploit this type of structure as part of its function. What we believe is that this type of structure can actually be used as a signal inside the genome to turn genes on and off, and to act as kind of a switch, because we see that the structure can form dynamically, so it can appear and disappear in response to different conditions, or different stages of the cell cycle.

Sputnik: Can you talk about the functionality of this, what do you know so far?

Marcel Dinger: We actually know very little so far, except to say that different kinds of DNA structures in other environments and systems can be used as switches, so that's something that's known in biology, so this really gives a new mechanism or a new way that the genome can control the behavior, or potentially regulate the behavior of genes, and that's something where the next research will start to be focused on, to actually decipher and understand what the functions might be of these structures. What we've really done now is we've really opened up new branches of DNA biology and DNA science.

Sputnik: What are your thoughts on how significant this could be to perhaps understanding the way genes are turned on and off? What could be the relationship to telomeres and the process of aging?

Marcel Dinger: What we want to do next now in terms of the research is to identify exactly where these i-motifs are formed in the genome. With the antibody that we've developed we can actually specifically target and potentially pull down the sequences of DNA that form i-motif, and then identify the genome might. And that's where we'll really move forwards in the study, that will also tell us exactly where they are, their relationship is, and where their proximity is to gene, and where they're positioned precisely in the telomeres. It certainly is intriguing that they're enriched in telomeric regions, but at this stage it's too early for us to say it's just a coincidence, because telomeric regions have the right sequence composition that enables i-motif formation; we simply don't know yet what that might mean, but it may help us unravel the functions of telomeres and what their potential roles, why telomeres are regarded as having this role in ageing and defining the age of our cells in our bodies.

Sputnik: What do you think are the primary practical applications that we can hope to gain from this discovery? Marcel Dinger: This is a structure, so structures when they're as specific as this, they can potentially be targeted by different sorts of therapeutics. What that means, is that if we can understand how an i-motif turns a gene on an off, we can potentially develop drugs or therapies that actually target i-motifs and regulate their behavior; so it's another way that we can potentially treat disease, understand the functions of disease, they may have really quite important roles in biotechnological applications and in bioengineering and so on. Another area is because we understand the composition of the sequence that's required, the specific combination of letters of DNA that can form i-motif, we also can understand if there are mutations in those parts of the genome, between individuals, that can also help us understand more about variations in our genomes.

Sputnik: Now having found this new structure, do you feel like we still have a lot to learn about DNA and human genetics, and there probably could be more structures that we haven't discovered yet?

Marcel Dinger: Totally, even though we can read the DNA sequence now, actually don't understand what most of the sequence means, 97-98% of the genome is unknown, only 1 to 2% we can decipher and understand. Understanding a structure like this certainly adds to that and contributes to our understanding of the genome, but we have a really, really long way to go and I don't doubt that there are other structures and formations that DNA can take and those actually have intrinsic functions.

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