The human body confirms the existence of new DNA structures or has a major association with human aging and cancer.
Release date: 2018-05-28
It has been 65 years since we discovered the DNA double helix.
On April 25, 1953, Nature published a landmark paper that first introduced the double helix structure of DNA to humans. The advent of this article is like a mantra that opens the door to the mysterious door of life sciences. People can see the secret of life. Since then, life phenomena that were previously considered unexplained have become clear, and various biological breakthroughs have followed.
Nowadays, the double helix structure of DNA has become a major discovery in the history of human civilization. Scientists have not stopped exploring the structure of DNA, because every new discovery has the potential to change the course of life science.
Recently, scientists from the Canadian Gavin Medical Institute confirmed for the first time a new DNA structure in human living cells: i-motif. This newly confirmed structure resembles a distorted DNA "knot", and this new discovery was published in the April 23 issue of Nature-Chemology.
Prior to this discovery, humans have never detected this structure directly in living cells.
“When most of us think of DNA, we think of a double helix,†said Daniel Christ, an antibody therapist at the Canadian Gavin Medical Institute. “But this new study reminds us that there are still completely different creatures. DNA structure, and these structures are likely to be very important to our cells."
The team referred to this new DNA structure as an "i-motif" structure. It should be noted that this structure was first discovered by researchers in the 1990s.
However, at the time, scientists believed that the environment favored by i-motif could be created in the laboratory, but it does not seem to occur naturally in the body, so scientists believe that it cannot exist in human cells. Moreover, before this discovery, scientists only saw it in vitro, not in living cells. Therefore, people have been questioning the meaning of this structure.
Now, thanks to the Christ team, we know that i-motif naturally exists in human cells, which means that scientists should pay attention to the importance of this structure to cell biology.
The new structure i-motif is a DNA four-strand "knot". Marcel Dinger, co-author of the study's genomics and head of the Calvin Clinical Genomics Research Center, explains: "In this 'knot' structure, C (cytosine) on the same DNA strand binds to each other; in a double helix In the middle, the bases on the two opposite chains recognize each other, and C is combined with G (guanine), which is quite different."
According to Mahdi Zeraati, the first author of the new study and the Canadian Institute of Medicine, i-motif is one of many DNA structures that do not use a double helix. Other DNA structures including A-DNA, Z-DNA, triple-stranded DNA, and cruciform DNA may also be present in our cells, however, these structures have not been confirmed.
In 2013, researchers also observed another DNA structure called G-quadruplex (G4) in human cells for the first time, and used genetically engineered antibodies to show that G4 is present in cells. This structure is the first DNA structure to be confirmed in human cells in addition to the double helix structure.
The new study also uses the same technology as in 2013. Specifically, the researchers developed an antibody fragment that specifically recognizes and binds to i-motif, called "iMab", and then by fluorescence immunoassay. iMab marks the location of the i-motif.
Dinger said that what really fascinates the team is not only the presence of these i-motifs in living cells, but also the twinkling green light. Team member Zeraati said: "We can see that the green spots (i-motif) disappear and disappear over time, which tells us that they are forming, disappearing, and re-forming."
The extinction of these spots means that the i-motif fold appears and disappears, and it repeats. In particular, the researchers also found that DNA is more efficiently folded into i-motifs at specific transcriptional stages (genes begin to be converted to proteins), ie when DNA is just beginning to actively transcribe. Then, the DNA stretches back to its usual form, and the i-motif disappears. According to Dinger, this may mean that i-motif plays a very special role in the transcription process.
For the time being, i-motif is usually formed in the late stages of the cell's life cycle, when DNA is actively "read". I-motif also tends to have a "promoter region" that controls the opening and closing of genes. At the same time, i-motif also tends to appear in telomeres, while telomeres are closely related to aging.
However, although researchers have already known the regions and time points at which these folded DNAs may occur, they do not know which genes they control, nor what consequences if they are interrupted by human intervention.
With this information, scientists speculate that i-motif seems to help turn genes on or off and is related to whether genes are actively read. The disappearance of the formation of i-motif also seems to explain why they were previously difficult to detect in cells.
However, confirming this new structure is only a new beginning, and there is still a lot of knowledge about the operation of the i-motif structure. Zeraati said: "We believe that we can discover its function from these dynamic processes of i-motif. It seems likely to help open and close genes and affect whether genes can be actively read."
Now, with a clear understanding of the existence of this new form of DNA in cells, researchers will try to figure out the role of these structures in our bodies.
"The deformed DNA conformation is important for proteins in cells to recognize their homologous DNA sequences and exert their regulatory functions," Zeraati said. "Therefore, the formation of these structures may be critical for cells to function properly." Moreover, any distortion in these structures can produce pathological results."
As Zeraati explains, the answer to this question can be very important. It involves not only i-motif, but also A-DNA, Z-DNA, triple-stranded DNA and cruciform DNA.
“We still know very little about the genome, and we may even know only one percent,†Dinger said. Seeing such a DNA structure in living cells “makes it possible to decode and understand the role of this genome. ".
Indeed, these strange folds may exist in each of our cells. In this regard, Dinge r said that DNA-targeted drugs may be more specific than their conventional forms of DNA, and these drugs may include drugs that help treat cancer.
Laurence Hurley, a professor at the University of Arizona and chief scientific officer at Reglagene, says one of the problems in treating certain cancers is the lack of selectivity in targeting the problematic DNA fragments. Not only that, but these drugs may also attach to other parts of the DNA, which can cause harmful side effects. Hurley is not involved in this new study.
Hurley said: "I have been waiting for such findings for a long time. They provide a solid foundation for major therapeutic efforts around these new structures and eliminate doubts about the existence and significance of these structures."
Unlocking the mystery of the function of the new DNA structure, we may enter a new era of life sciences, as Dinger puts it: “It is very exciting to discover a new form of DNA in cells! These findings It will lay the groundwork for research on the function of new forms of DNA and its impact on health and disease."
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