Twisted Knot-Shaped DNA Discovered in Human Living Cells

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Twisted Knot-Shaped DNA Discovered in Human Living Cells

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Researchers at Garvan Institute of Medical Research up the bar with a breakthrough discovery since the iconic DNA double-helix structure by Cambridge University scientists James Watson and Francis Crick 65 years ago. The research declared that DNA shape isn’t always “double-stranded” but also “knot-twisted.”

Recent findings published in the journal Nature Chemistry called the new DNA structure i-motif which appeared similar to a “twisted knot” and was seen inside the living cells for the very first time.  

Daniel Christ, head of the Antibody Therapeutics Lab at Garvan and co-lead of the research said, “When most of us think of DNA, we think of the double helix. This new research reminds us that totally different DNA structures exist and could well be important for our cells.”


The Double-Helix DNA

The DNA or deoxyribonucleic acid is the molecule which contains human genes where information needed to live, grow, and multiply are stored in the living cells. All 6 billion A (adenine), C (cytosine), G (guanine) and T (thymine) bases are DNA codes which accurately dictate the genetic blueprint of life. It is shaped like a twisted ladder or “double helix” and is indispensable for our survival.

DNA was actually discovered in 1869, it’s genetic inheritance was determined in 1943 and its structure, the famous double helix was known in 1953 courtesy of Watson and Crick.

In the book, “Double Helix” published in 1968, Watson explained their findings that DNA replicated itself by separating into individual strands. Each strand became another template to form new double helix.

Crick announced their discovery in between blurts in a pub that “they have discovered the secret of life.” This claim actually rang scientific bells since they were able to solve humanities’ mysteries for organisms to pass on genetic instructions from generation to the next.

Their findings revolutionized fields of biology and medicine which were seen and felt  in the prenatal screening of disease genes, genetically engineered foods, treatment designs for diseases such as AIDS, in forensic science for identification of human remains, and for assessment of physical evidence in a crime scene investigation (CSI) which could convict or exonerate a suspect of a crime.


A twisted ‘knot’ of DNA, the i-motif has never before been directly seen inside living cells. Image credit: Zeraati et al,


I-Motif Structure

Today’s science can now say with certainty that DNA in short tracts exist in other shapes. The shape is completely different than the “double-stranded, double helix.”

Scientists in the Lab revealed presence of green spots called i-motifs which appeared and disappeared during the process of observation. They suspected that these shapes were actually forming, dissolving and forming again over time. And that they were presumed to play important role or function in the “reading” of the DNA code.

"We also think the transient nature of the i-motifs explains why they have been so very difficult to track down in cells until now," said Prof. Christ.

The research was able to identify when the i-motifs appear in a cell’s life cycle. In their observation, i-motifs form at the late phase of the G1 when the DNA is actively “being read.”

Dr. Mahdi Zeraati, co-lead of the research said, "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.”

"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," he added.

The i-motifs were also seen in the promoter regions or areas of DNA where genes are controlled or switched on or off. Also, in the end sections or “telomeres”  of the chromosomes responsible for the aging process.

The research team was ecstatic over the unveiling of whole new form of DNA cells.  They are looking at this discovery as a precursor for further research to fully understand what the i-motif shape is meant for and its possible impact on diseases and overall health.


An illustration of an i-motif embedded in a strand of DNA. Credits: Mahdi Zeraati


Identifying the I-Motif

The lab process entailed observation in living cells, a first milestone in the study of DNA. In order to detect, locate and identify i-motifs DNA,  the researchers designed tiny probes which recognized the DNA knots.

The tiny probes were created using a fragments of an antibody molecule, the Y-shaped  molecule with specific substances. For the benefit of the experiment, the antibody was engineered so its behavior would attach itself to i-motifs alone. In this case, the antibody was engineered so that it would recognize and attach itself to i-motifs but not to any other form of DNA.

Researchers used the fluorescence techniques (dye) in order to espy the location of the i-motifs in the human cell landscape. The process assisted the researchers to look into numerous green spots within the nucleus. The function of these knot-twisted shaped DNA is yet to be determined. But researchers surmised that it could be involved with the “reading” of the DNA sequences and converting them to useful substances in the body.

Professor Marcel Dinger, the study’s other co-leader explained that “The i-motif is a four-stranded ‘knot’ of DNA, wherein the knot structure, C [cytosine] letters on the same strand of DNA bind to each other. This is so different from a double helix, where ‘letters’ on opposite strands recognise each other, and where Cs bind to Gs [guanines].”



Kay Yeban

Twisted Knot-Shaped DNA Structure Discovered in Human Living Cells