A new “tangled” form of DNA has been uncovered in living cells

It’s DNA, but not as we know it. By studying short stretches of DNA, and using an antibody molecule, researchers from Australia have discovered a new DNA structure buried inside living cells.

Called i-motif, the structure builds on the double helix shape commonly associated with DNA and has been described as a type of “twisted knot” that has, until now, only been seen in artificial cells.  

Double helix and the i-motif

 Since 1953, when James Watson and Francis Crick uncovered the structure of DNA, we’ve known that our genetic code, made up of 6 billion A, C, G and T letters, creates a shape known as a double helix. Previous lab-based studies have identified other forms of structures found in our DNA, using artificial conditions, including the i-motif “knot”, but the unusual structure has never before been witnessed and studied inside living cells. 

In fact, scientists have debated whether i-motif ‘knots’ would exist inside living things at all. It’s still not known if the structure exists in living cells outside of laboratory conditions, but it is thought that if the i-motif does occur naturally within our bodies, for example, it could play a key role in how and when DNA code is “read.”

“When most of us think of DNA, we think of the double helix,” said associate professor Daniel Christ from Garvan Institute of Medical Research. “This new research reminds us that totally different DNA structures exist – and could well be important for our cells.”

The i-motif differs because it’s a four-stranded ‘knot’ of DNA. In the knot structure, C letters on the same strand of DNA bind to each other meaning this discovery is very different from a double helix, where ‘letters’ on opposite strands recognise each other.

Identifying the i-motif

dna_nanorobots_cancer

To detect i-motifs inside cells, the researchers developed a fragment of an antibody molecule that could specifically recognise and attach to i-motifs. This helped researchers uncover the location of ‘i-motifs’ in a range of human cell lines. Using fluorescence techniques to pinpoint exactly where the i-motifs were located, the team identified numerous spots of green within the nucleus.

“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,” said Dr Mahdi Zeraati, whose research underpins the study’s findings. “We think the coming and going of the i-motifs is a clue to what they do. 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.”

In particular, 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’. They also showed that i-motifs appear in areas of DNA that control whether genes are switched on or off, and in telomeres, ‘end sections’ of chromosomes that are important in the ageing process.

“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,” explained associate professor Marcel Dinger. 

The new findings are published in the journal Nature Chemistry.

Image: Chris Hammang

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