If you still remember your high school biology, you’ll be pretty familiar with the classic double helix shape of DNA.
But did you know that there are parts of your strands of DNA that don’t follow this shape; and instead they form a kind of knot (also known as i-motifs) along the many genetic threads that make up the human genome.
These odd structures were first noticed by researchers in 1993, but they weren’t properly identified until 2018.
Now, researchers at the Garvan Institute have discovered that there are actually 50,000 of these i-motifs in the human genome; they have since mapped the locations of these in human DNA.
Going back to that high school biology, perhaps you’ll remember the four bases of a molecule of DNA. The bases are known as adenine (A), cytosine (C), guanine (G), and thymine (T).
‘Normal’ DNA molecules have two strands winding round in that double helix shape, and the strands are bonded by the pairing of the bases.
Adenine pairs up with thymine to form the A-T bond, whereas cytosine pairs up with guanine, forming the C-G bond.
In the case of i-motifs, however, the irregularities in the double helix occur because of unusual bonding. These structures form where cytosine has paired with itself, in a C-C bond.
Instead of the classic double helix, this results in a twisting of the structure.
The identification of the 50,000 i-motifs, the researchers suggest, shows that this C-C bond is far less irregular than we might think. Professor Daniel Christ, senior author on the study, explained the importance of these new findings in a statement from the Garvan Institute:
“In this study, we mapped more than 50,000 i-motif sites in the human genome that occur in all three of the cell types we examined. That’s a remarkably high number for a DNA structure whose existence in cells was once considered controversial. Our findings confirm that i-motifs are not just laboratory curiosities but widespread – and likely to play key roles in genomic function.”
So, the i-motifs are not an anomaly: instead, the researchers believe, they have specific purposes in the body. In particular, there is a high number of i-motifs in areas of the genome that carry out specific purposes.
While this is interesting in itself, it could also be key to future medical breakthroughs, including the targeting of deadly diseases.
In the statement, Cristian David Peña Martinez, first author of the study – which was published recently in The EMBO Journal, explains how the team’s research could be pivotal in the fight against certain types of cancer:
“We discovered that i-motifs are associated with genes that are highly active during specific times in the cell cycle. This suggests they play a dynamic role in regulating gene activity.
We also found that i-motifs form in the promoter region of oncogenes, for instance the MYC oncogene, which encodes one of cancer’s most notorious ‘undruggable’ targets. This presents an exciting opportunity to target disease-linked genes through the i-motif structure.”
In particular, this could influence the way in which we treat these cancers.
By understanding that they could be caused by specific i-motifs in the genome, scientists will be able to design treatment programs that are able to adapt the way that the i-motifs are expressed in human DNA.
Co-author of the study Sarah Kummerfeld, explains how fresh treatment prospects could be developed as a result of this:
“The widespread presence of i-motifs near these ‘holy grail’ sequences involved in hard-to-treat cancers opens up new possibilities for new diagnostic and therapeutic approaches. It might be possible to design drugs that target i-motifs to influence gene expression, which could expand current treatment options.”
These new treatment programmes are a long way off, but the important work of researchers at the Garvan Institute in mapping i-motifs and understanding their role in human health could signal hope for the future.
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