Last updated April 24, 2018 at 1:50 pm
A totally new DNA structure called the i-motif forms, dissolves and forms again.
Even the smallest of packages can have the biggest surprises. Scientists have finally identified a twisted knot of DNA, the i-motif, inside living cells. This new shape is a four-stranded knot of DNA.
DNA is known for its iconic double helix shape but DNA is not bound to just one configuration.
While DNA takes on its double helix form to efficiently store the genetic code, it also needs to adopt structural changes when that information needs to be accessed.
Scientists have previously known about and seen the existence of i-motifs for a while but this is the first time scientists have witnessed it inside a living cell. This resolves previous doubts about whether the i-motif would exist inside living things.
“This new research reminds us that totally different DNA structures exist – and could well be important for our cells,” says Daniel Christ, who co-led the research.
Finding the i-motif
To find the mysterious i-motif, researchers created an antibody fragment that was able to recognise i-motif structures within the nucleus of a human cell.
It was able to do this with high selectivity and affinity, meaning that it wouldn’t bind to anything else and it would bind strongly to the i-motif to allow for it to be detected.
DNA code contains A, C, G and T (which represent different nucleotide bases). Some regions of DNA are known to contain higher numbers of certain base pairs.
From previous in vitro studies, researchers knew that i-motif structures are more common in C-rich regions such as the telomeres, and other regulatory regions.
Thanks to their antibody fragment, researchers were able to show that i-motifs could be found in regulatory regions like the telomere, as well as promoter regions that control whether genes are switched on or off. Telomeres make up the caps of chromosomes and are known to be associated with ageing.
Clues hint at i-motif function
“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, whose research underpins the study’s findings.
They were also able to show that i-motif formation was dependent on cell-cycle progression and pH variation. The researchers showed that i-motifs mostly form at a particular point in the cell’s ‘life cycle’ – the late G1 phase, when DNA is being actively ‘read’.
“We think the coming and going of the i-motifs is a clue to what they do,” Dr Zeraati says. “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.”
“The transient nature of the i-motifs explains why they have been so very difficult to track down in cells until now,” adds A/Prof 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 co-author Marcel Dinger.
The research is published in Nature Chemistry.
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