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New four-stranded structure that comes and goes in the DNA

24 April 2018

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.

And if finding out that you have a completely unique and never before seen structure in your DNA is somewhat of a shock, then it must be completely mind-blowing to fathom that there could be others as well. Crucially, the tool ignored sections of DNA in its usual double helix form, as well as other structures.

A team of Australian researchers at Sydney's Garvan Institute has identified a knotty version of DNA, known as an I-motif, that appears within DNA when it is actively being read. In any case, it's now realized that short extends of DNA can exist in different shapes, in the lab at any rate - and researchers presume that these diverse shapes may assume an imperative part in how and when the DNA code is "read". Scientists from the Garvan Institute of Medical Research have made this discovery by directly seeing i-motif inside living cells.

The double helix shape of DNA has been around since 1953 but the new research reveals that in short stretches DNA can take other shapes and scientists believe that the different shapes might play an important role in how and when the DNA code is "read".

"When most of us think of DNA, we think of the double helix", says Associate Professor Daniel Christ (Head, Antibody Therapeutics Lab, Garvan) who co-led the research.

The new find has been called the "twisted knot" of DNA, and it shows just how complex human DNA is beyond the modern understanding of a double-helix structure.

The scientists observed that these structures tend to form later in the cells' life cycle and that they particularly appear in the areas of our DNA responsible for determining whether genes are activated or turned off.

To detect i-motifs inside cells, the researchers developed a fragment of an antibody molecule that could specifically recognise and attach to i-motifs. Genetics 101 says that DNA follows some strict base-pairing rules where adenine (A) always binds to thymine (T), and cytosine (C) always hooks up with guanine (G).

The I-motif was not detectable all the time.

To be clear, not just any piece of DNA can fold itself into the four stranded i-motif shape. It mostly stayed away from the parts that code for proteins, and instead was involved in regulatory regions that switch genes on and off (promoters) and telomeres (chromosome tips). Utilizing fluorescence methods to pinpoint where the I-themes were found, they recognized various spots of green inside the core, which show the situation of I-motifs.

The recent research was published in the most recent edition of the journal Nature Chemistry.

Zeraati said, "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".

"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.

New four-stranded structure that comes and goes in the DNA