DNA detail displayed
Australian researchers have identified a new DNA structure that has never before been directly seen inside living cells.
The iconic ‘double helix’ shape of DNA is well known, but it is not as well known that short stretches of DNA can exist in other shapes, in the laboratory at least.
Scientists have suspected that these different shapes might play an important role in how and when the DNA code is ‘read’.
The new shape looks entirely different to the double-stranded DNA double helix.
“When most of us think of DNA, we think of the double helix,” says Associate Professor Daniel Christ from 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 new DNA structure – called the i-motif – is formed in a twisted ‘knot’ shape.
“The i-motif is a four-stranded ‘knot’ of DNA,” says researcher Dr Marcel Dinger.
“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].”
Although researchers have seen the i-motif before and have studied it in detail, it has only been witnessed in vitro, not inside cells.
In fact, scientists in the field have debated whether i-motif ‘knots’ would exist at all inside living things – a question that is resolved by the new findings.
To detect the i-motifs inside cells, the researchers developed a precise new tool – a fragment of an antibody molecule – that could specifically recognise and attach to i-motifs with a very high affinity.
Until now, the lack of an antibody that is specific for i-motifs has severely hampered the understanding of their role.
Crucially, the antibody fragment didn’t detect DNA in helical form, nor did it recognise ‘G-quadruplex structures’ (a structurally similar four-stranded DNA arrangement).
With the new tool, researchers uncovered the location of ‘i-motifs’ in a range of human cell lines. Using fluorescence techniques to pinpoint where the i-motifs were located, they identified numerous spots of green within the nucleus, which indicate the position of i-motifs.
“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.
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 some promoter regions (areas of DNA that control whether genes are switched on or off) and in telomeres, ‘end sections’ of chromosomes that are important in the aging process.