HEALTH

BREAKING: Scientists Have

Confirmed a New DNA
Structure Inside Human
Cells
It's not just the double helix!
PETER DOCKRILL
23 APR 2018
For the first time, scientists have identified the existence
of a new DNA structure never before seen in living cells.

The discovery of what's described as a 'twisted knot' of

DNA in living cells confirms our complex genetic code is
crafted with more intricate symmetry than just the double
helix structure everybody associates with DNA – and the
forms these molecular variants take affect how our
biology functions.

"When most of us think of DNA, we think of the double

helix," ​says antibody therapeutics researcher Daniel
Christ​ from the Garvan Institute of Medical Research in
Australia.
"This new research reminds us that totally different DNA
structures exist – and could well be important for our
cells."

The new DNA component the team identified is called

the ​intercalated motif​(i-motif) structure, which was first
discovered by researchers ​in the 1990s​, but up until now
had only ever been witnessed ​in vitro​, not in living cells.

Now, thanks to Christ's team, we know the i-motif occurs

naturally in human cells, meaning the structure's
significance to cell biology – which has previously been
called into question, given it had only been demonstrated
in the lab – demands new attention from researchers.
(Zeraati et al., Nat Chem, 2018)

If your only familiarity with DNA shapes is the ​dual helical

spirals​ made famous by Watson and Crick, the
configuration of the intercalated motif could come as a
surprise.

"The i-motif is a four-stranded 'knot' of DNA," ​explains

genomicist Marcel Dinger​, who co-led the research.

"In the knot structure, C [cytosine] 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]."

According to Garvan's Mahdi Zeraati, the first author of

the new study, the i-motif is only one of a number of DNA
structures that don't take the double helix form –
including A-DNA, Z-DNA, triplex DNA and Cruciform
DNA – and which could also exist in our cells.

Another kind of DNA structure, called G-quadruplex (G4)

DNA, was first visualised by researchers in human cells
in 2013​, who made use of an engineered antibody to
reveal the G4 within cells.

In the new study, Zeraati and fellow researchers

employed the same kind of technique, developing an
antibody fragment (called iMab) that could specifically
recognise and bind to i-motifs.

In doing so, it highlighted their location in the cell with an

immunofluorescent glow.
Artist's impression, overlaid on imaging of the iMab antibody (green) in the nuclei of
cells (Chris Hammang)

"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 Zeraati​.

While there's still a lot to learn about how the i-motif

structure functions, the findings indicate that transient
i-motifs generally form late in a cell's 'life cycle' –
specifically called the late ​G1 phase​, when DNA is being
actively 'read'.

The i-motifs also tend to appear in what are known as

'promoter' regions​ – areas of DNA that control whether
genes are switched on or off – and in ​telomeres​, genetic
markers associated with ageing.

"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."

Now that we definitively know this new form of DNA

exists in cells, it'll give researchers a mandate to figure
out just what these structures are doing inside our
bodies.

As Zeraati explains, the answers could be really

important – not just for the i-motif, but for A-DNA, Z-DNA,
triplex DNA, and cruciform DNA too.

"These alternative DNA conformations might be

important for proteins in the cell to recognise their
 cognate DNA sequence and exert their regulatory
functions," Zeraati explained to ScienceAlert.

"Therefore, the formation of these structures might be of

utmost importance for the cell to function normally. And,
any aberration in these structures might have
pathological consequences."

The findings are reported in ​Nature Chemistry.​

Link to Website:
https://www.sciencealert.com/scientists-have-confirmed-a-new-dna-structure-inside-livin
g-cells-i-motif-intercalated