The discovery of DNA as a double helix is a sacred history of scientific triumph – the work of four researchers who unite to solve one of the greatest puzzles of science and create what we know to be the field of modern genetics , But decades later, we still learn that DNA is an even more complicated piece of biological machinery than we've ever known.
For the first time, scientists have just discovered a new form of DNA lurking in human cells. In a study published in Nature Chemistry on Monday, a team of researchers from the Kinghorn Center for Clinical Genomics at the Garvan Institute for Medical Research in Sydney described the discovery of DNA as a four-stranded nodule-like structure. In human cells, much of what we thought earlier could and could not exist in living people, and a number of questions about the role of this structure could be, if it has one at all.
We already know DNA can come in other forms, such as triple helices or cruciforms. And the i-motif is not the first four-stranded structure in human cells; Scientists did that in 201
"This has led to a scientific debate on the biological relevance of this motif," says Daniel Christ, director of the Targeted Therapy Center at the Garvan Institute and co-author of the new study. "We provide initial direct evidence that the i-motif structure exists in cells under physiological conditions."
Here's how the i-motif works: Imagine a small stretch of DNA double helix where the hydrogen bonds connect the two main chains. The strands break away as the helix suddenly turns up. If one of the strands is full of cytosine (one of the four major nucleic acids that comprise DNA), it will move outward like a tied-up shoelace. Hydrogen bonds form within the loop itself and bind these cytosines together (rather than guanine, as is usually the case with the double helix).
"They essentially form a scaffold in which every CC bond is 90 degrees. The corresponding CC pair," says Laurence Hurley, a medical chemist at the University of Arizona, who also studied i-motives.
To confirm the presence of these i-motifs in human DNA and to determine their locations, the Sydney team has created a special fragment of an antibody molecule that can bind to the i-motif structure. They then used fluorescence techniques to highlight the antibody molecules under the microscope. It is a very tried and tested method in chemistry and biology, and should eliminate doubts about the truthfulness of these i-motives in nature.
But what does the i-motive do? There is some evidence that it plays a role in transcription (when the cell uses DNA as a guide to making various proteins). The Sydney team investigated the presence of i-motifs during all phases of the cell cycle and found that motifs are most common when DNA is actively transcribed, but it disappears when DNA is replicated.
They also found the motifs often appeared in parts of the promoter regions genes that are not read and expressed as protein products, but instead can turn on and off the expression of other genes and prevent or promote the production of certain proteins. "We think it is likely that the formation of i motifs in promoter regions fine tunes the expression of corresponding genes," says Christ.
According to Hurley, there are specific proteins and mechanisms that dissolve the DNA, generate the i-motif folds and stabilizes them during transcription, and then unfolds this knotty loop and brings things back into a double helix, though it's time for cell division. And this can be accomplished without the super-acidic adjustment typically required for these subjects. "That's where the power of these structures lies," he says. "They are highly dynamic, and you can fold and unfold them to activate transcription."
"It is clear that these structures [i-motifs] are involved in gene expression," says Hurley. "This essay delivers the icing on the cake."
Hurley and others have previously found evidence that i-motifs are associated with a number of cancer-related genes, such as MYC (expressed in over 80 percent of cancers), KRAS (which controls cell growth and cell proliferation), and BCL-2 (which prevents cancer from undergoing apoptosis or programmed death). Hurley himself has recently formed a new company, Reglegen, which seeks to use these i-motives as potential targets for new cancer drugs and to prevent oncogenesis at the genetic level itself, as opposed to "inedible" protein targets.
Recent findings show quite convincingly that i-motifs can emerge in living human cells. Hanbin Mao, a biochemist at Kent State University who was not involved in this study, notes that there is more compelling evidence that i-motifs are a natural phenomenon. The Sydney researchers can not say with certainty that the antibody does not bind to other targets and, more importantly, that the binding of the antibody to the DNA does not promote the formation of I-motif itself. Needless to say, there is research from years or even decades to learn more about what i-motives are, how they work, why they exist, and how we can use their powers  Almost 65 years after Watson, Crick , Franklin and Wilkins continue to compress the DNA plot.