“I-motif” – A Completely New DNA Structure In Human Cells

  • Scientists found a new DNA structure, named i-motif, in human cells. 
  • They have built an accurate fragment of an antibody molecule to recognize i-motif’s structure.
  • It’s a four-stranded knot of DNA, where C letters (cytosine) on the same DNA strand bind to each other.

For the first time, researchers at the Garvan Institute of Medical Research, Australia, have detected a new structure of DNA, named i-motif, in human cells. It’s described as “twisted knot” of DNA – a form that has never been directly observed in the nuclei of human cells.

DNA (Deoxyribonucleic Acid) is made up of nucleotide molecules, which contain adenine (A), cytosine (C), guanine(G) and thymine (T). The order of these four determines genetic code, which provides accurate instruction for how human bodies are formed and how they work. Human DNA has approximately 3 billion bases, of which 99% are same in all people.

DNA has a “double helix” structure, which was first uncovered by Francis Crick and James Watson in 1953. Now scientists have observed something different than this old structure. In laboratory tests, they identified new short stretches of DNA that can play a crucial role in when and how the code of DNA is ‘read’.

How I-motif is Different Than Double Helix DNA?

It’s a four-stranded knot of DNA, where C letters (cytosine) on the same DNA strand bind to each other. Whereas in double helix DNA, C binds to G (guanine), and opposite strand letters recognize each other.

The two parallel duplexes make a quadruplex structure. I-motif is stable in acidic environment, but starts to become unstable in neutral or basic solutions. Also, it’s rich in uncommon C-C (cytosine-cytosine) bonds.

Scientists have already observed this i-motif DNA structure — in a research done in 2014 — but under artificial environments in the lab. This time, they’ve identified it in an actual human cell.

Because of i-motif’s pH dependent folding, its DNA sequences have been used as pH switches for nanotech applications. Initially, i-motif was thought to be unstable at physiological pH. However, new studies have made it clear that this isn’t always the case. The stability of i-motif depends on parameters like sequence and surrounding scenarios.

How Did They Identified It?

Schematic of i-motif and G4 structures  | Credit: Garvan Institute of Medical Research 

Scientists built an accurate fragment of an antibody molecule to recognize i-motif’s structure. Also, i-motifs could be attached to this newly developed fragment with high affinity. Before this, the lack of i-motif-specific antibody hampered our understanding of its functionalities.

Reference: Nature Chemistry | doi:10.1038/s41557-018-0046-3 | Garvan Institute 

However, the fragment did not recognize DNA in 4-stranded structure, called G quadruplex structure, nor did it identify DNA in helical shape. It helped scientists to precisely locate the i-motif in human cell lines.

They detected several green spots inside the nucleus, by applying fluorescence methods. These spots show the precise location of i-motifs.

What’s even more interesting is, they saw spots were appearing and disappearing at irregular intervals. This means that i-motifs were forming and dissolving over time.

They mostly formed (while DNA is being ‘read’) at the late G1 phase – a specific location in the cell. Also, they were detected in the endpoints of chromosomes, called telomeres (key to aging) and in a few promoter areas that decide whether genes are switched off or on.

Read: Programmed DNA Nanorobots Can Reduce Tumor

The results provide a core foundation for future researches scrutinizing the key function of this genomic DNA structure, and for validation as a therapeutic target in pathological scenarios like cancer.

Written by
Varun Kumar

Varun Kumar is an experienced science and technology journalist interested in machines, AI, and space exploration. He received a Master's degree in computer science from Indraprastha University. To find out what his latest project is, feel free to directly email him at [email protected] 

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