Unexpected DNA Knots: How 50,000 Mysterious Twists Could Unlock Cures for Diseases Like Cancer

by Abbas Adil

Shafaqna Science:  An innovative study of DNA’s hidden structures could lead to new ways of diagnosing and treating diseases like cancer.

Researchers at the Garvan Institute have created the first detailed map of over 50,000 i-motifs in the human genome—structures that differ from the classic double helix and may play key roles in gene regulation and disease. These findings suggest that i-motifs could be vital in developing new therapies, particularly for targeting genes linked to cancers.

Uncovering the Role of DNA i-Motifs

While DNA is famous for its double helix shape, researchers at the Garvan Institute of Medical Research have discovered more than 50,000 unusual ‘knot’-like DNA structures called i-motifs within the human genome.

Published today (August 29) in *The EMBO Journal*, the first comprehensive map of these unique structures sheds light on their potential roles in regulating genes involved in disease.

In a groundbreaking 2018 study, Garvan scientists were the first to directly observe i-motifs inside living human cells using an antibody they developed to specifically recognize and bind to these structures. The current research expands on these findings by using this antibody to identify i-motif locations throughout the entire genome.

Mapping DNA’s Knot-Like I-Motifs

The i-motif, a knot-like structure that extends from DNA’s double helix, has been mapped in 50,000 locations in the human genome, particularly in regions that regulate gene activity. “In this study, we mapped more than 50,000 i-motif sites in the human genome that appear in all three cell types we examined,” says senior author Professor Daniel Christ, Head of the Antibody Therapeutics Lab and Director of the Centre for Targeted Therapy at Garvan. “That’s a remarkably high number for a DNA structure once considered controversial. Our findings confirm that i-motifs are not just laboratory curiosities but are widespread and likely play crucial roles in genomic function.”

The Importance of i-Motifs in Gene Regulation

I-motifs are DNA structures distinct from the well-known double helix. They form when cytosine-rich regions on the same DNA strand pair up, creating a four-stranded, twisted structure that protrudes from the double helix.

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