In a first, researchers at Garvan Institute of Medical Research, Australia have identified a new DNA structure inside living human cells. Known as the intercalated motif (i-Motif), the newly identified structure looks poles apart from the iconic double helix shape everyone associates with DNA.
”When most of us think of DNA, we think of the double helix,” says Associate Professor Daniel Christ Head of Antibody Therapeutics Lab, Garvan, in a statement. “This new research reminds us that totally different DNA structures exist — and could well be important for our cells.”
The i-Motiff is a four-stranded knot of DNA. The structure, in fact, was first discovered in the early 90s, but, it had only been seen in vitro, and not inside living cells. Researchers even argued whether it would exist at all inside living things. But thanks to new findings, its existence has now been confirmed.
DNA stores genetic information in sequences of four bases of nucleic acid — adenine, cytosine, guanine and thymine, which are abbreviated A,C, G and T. And according to our current understanding of double helix DNA, A pairs only with T, and C pairs only with G. However in this new DNA component, C letters on the same strand of DNA pairs to each other.
In the study, researchers developed a new tool (which is an antibody fragment) that could specifically recognise each other and attach to i-motifs. With it, they were able to pinpoint the location of ‘i-motifs’ in the human cell lines. They also identified several spots of green within the cells indicating the position of i-motifs – using fluorescence techniques.
“What excited us most is that we could see the green spots — the i-motifs — appearing and disappearing over time, so we know that they are forming, dissolving and forming again,” says Dr Mahdi Zeraati, the first author of the study.
According to their new findings, the i-motifs mostly form at the end of cell’s life cycle, that is, the late G1 phase, when DNA is being actively ‘read’. They also appear in some promoter regions (areas of DNA that control whether genes are switched on or off) and in telomeres, structures at the ends of chromosomes associated with the aging process.
“We think the coming and going of the i-motifs is a clue to what they do,” says Zeraati. “It seems likely that they are there to help switch genes on or off, and to affect whether a gene is actively read or not.”
“We also think the transient nature of the i-motifs explains why they have been so very difficult to track down in cells until now,” adds Christ.
“It’s exciting to uncover a whole new form of DNA in cells – and these findings will set the stage for a whole new push to understand what this new DNA shape is really for, and whether it will impact on health and disease.” says Associate Professor Marcel Dinger, who co-led the study with Christ and Zeraati.
The study has been published in the journal Nature Chemistry