Australian researchers have identified a new form of DNA structure known as an intercalated motif or "i-motif" inside living human cells.
The structure, described as a "twisted knot," may play an essential role in how and when DNA code is "read," researchers believe. Scientists first discovered the i-motif DNA component in the 1990s and even studied it in detail, but they had not seen the structure in living cells until now.
Daniel Christ and Marcel Dinger co-led the research at the Garvan Institute of Medical Research. The journal, Nature Chemistry, published the new findings on Monday.
“When most of us think of DNA, we think of the double helix,” Christ said in a news release. “This new research reminds us that totally different DNA structures exist — and could well be important for our cells.”
In 1953, James Watson and Francis Crick discovered the double helix DNA structure that many students learned about in biology class. The molecule is made up of two strands that appear similar to a twisted ladder. Its backbone consists of alternating sugar and phosphate molecules bonded by pairs of nucleotides: adenine (A), cytosine (C), guanine (G), and thymine (T). Adenine bonds with thymine and cytosine bonds with guanine.
How does i-motif DNA work?
The i-motif looks and works differently than the double helix.
“The i-motif is a four-stranded ‘knot’ of DNA,” Dinger said. “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 recognize each other, and where Cs bind to Gs [guanines].”
How was it discovered in living cells?
The researchers developed a precise tool, tiny fragments of antibody molecules, that could recognize and bind with the i-motif structures. The antibody fragments were engineered to detect and attach to i-motifs only, not any other DNA forms.
They used fluorescent green dyes on the antibodies to discover and monitor the DNA's location inside the nucleus of a variety of human cells.
“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.”
The nature of the i-motif could be the reason researchers have trouble locating it in live cells for so long.
“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," Dinger said.