Mysterious new form of DNA.
Mysterious new form of DNA seen inside human cells for the first time looks like a ‘twisted knot’ instead of a double helix
- Discovery of the ‘i-motif’ form of DNA was made by researchers in Sydney
- It is unclear what the function is but it could be for ‘reading’ DNA sequences
- Although researchers have seen the i-motif before, it has only been witnessed under artificial conditions in the laboratory, and not inside cells
A new form of DNA has been discovered inside living human cells for the first time.
Named i-motif, the form looks like a twisted ‘knot’ of DNA rather than the well-known double helix.
It is unclear what the function of the i-motif is, but experts believe it could be for ‘reading’ DNA sequences and converting them into useful substances.
The discovery was made by scientists from the Garvan Institute of Medical Research in Sydney.
Although researchers have seen the i-motif before, it has only been witnessed under artificial conditions in the laboratory, and not inside cells.
Scientists have previously debated whether i-motif ‘knots’ would exist at all inside living things – a question that is resolved by the new findings, published in Nature Chemistry.
‘When most of us think of DNA, we think of the double helix,’ said Associate Professor Daniel Christ, Head of the Antibody Therapeutics Lab at Garvan, who co-led the research.
‘This new research reminds us that totally different DNA structures exist and could well be important for our cells.’
The iconic ‘double helix’ was discovered in 1953 by James Watson and Francis Crick.
It is composed of four chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T).
The structure of the double-helix comes from adenine binding with thymine and cytosine binding with guanine.
‘In the knot structure, C letters on the same strand of DNA bind to each other – so this is very different from a double helix, where ‘letters’ on opposite strands recognise each other, and where Cs bind to Gs [guanines]’, said co-author Associate Professor Marcel Dinger, Head,of the Kinghorn Centre for Clinical Genomics at Garvan.
To detect the new i-motifs inside cells, researchers developed a new tool.
This was a fragment of an antibody molecule that could recognise and attach to i-motifs.
This antibody fragment did not recognise DNA in helical form and it did not recognise ‘G-quadruplex structures’ – which are structurally similar to four-stranded DNA arrangement.
With the new tool, researchers could uncover the location of ‘i-motifs’ in a range of human cell lines.
Using fluorescences techniques to pinpoint where the i-motifs were located scientists were able to identify numerous spots of green in 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.
They found that i-motifs formed at particular points in the cell’s ‘life cycle’ when the DNA is being actively ‘read’.
They also appear more in promoter regions, which are areas of DNA that control whether genes are switched on or off.
‘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’, said Dr Zeraati.
Researchers hope this finding will set the stage for a new push to understand what this new DNA shape is for and whether it will impact our understanding of health and disease.