The double helix structure of DNA has been known to all since its discovery in 1953 by James Watson and Francis Crick. But now, scientists are scratching their heads as a new form of DNA has been found inside human cells. Named i-motif, the form looks more like a twisted knot of DNA rather than the iconic double helix.

The discovery was made by scientists from the Garvan Institute of Medical Research in Sydney, Australia. The tangled shape had apparently been seen before under laboratory conditions, but few researchers expected it to occur in living human cells. The new work published in Nature Chemistry reports that not only do i-motifs indeed exist in human cells, they may be quite common.

“Our imaging suggests that this is a normal thing that happens”, said Marcel Dinger, a molecular biologist who oversaw the research. “It is very likely that genomes in all the cells of our bodies are forming i-motifs at some point in time.”

DNA is composed of four chemical bases: adenine (A), guanine (G), cytosine (C) and thymine (T). The double-helix structure comes from adenine binding with thymine and cytosine binding with guanine. DNA in our cells spends most of its time in this familiar double helix structure. But even in this stable shape, the molecule is constantly in flux. When a piece of DNA is being replicated, the two strands are pulled apart and paired with new sequences. DNA molecules also separate when the instructions for a gene are being read by the cell. When the process is over, the strands attach back together.

“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,” said Mr Dinger. In other words, not just any piece of DNA can fold itself into the i-motif shape. There must be a specific sequence of letters that include several cytosines. The four-stranded i-motif also only occurs in a relatively small region of a genome and sticks out like a bumpy knot in the smooth helical form.

It was back in the early 1990s when French scientists discovered that a cytosine-rich region of a DNA strand could fold on top of itself, creating a four-stranded shape in which Cs paired with Cs. Indeed, scientists have long known that DNA can fold into other forms in the laboratory including crosses and U shapes.

The question is, does DNA and its flexibility for taking on new shapes have any biological relevance? It is unclear what the function of the i-motif is, but it may play an essential role in human biology. Expect to hear much more about research into this subject soon.

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