25 April 2018

Mysterious DNA nodes

DNA inside a living cell can "tie in knots"

Anna Kerman, XX2 century

Biology textbooks may have to be rewritten. For the first time, a group of scientists discovered a section of DNA inside a living cell of the human body that resembles a four-core node, and not the double helix known to us all from school.

I-motif.jpg

Previously, such "nodules", called i-motifs, were observed only in laboratory conditions. However, some researchers suspected that they also occur in living cells. The new work has demonstrated that in the cells of the human body, i-motifs are not just found – they are quite widespread.

"The images we have indicate that this is normal,– says Marcel Dinger is a molecular biologist at the Garvan Institute of Medical Research in Sydney, Australia. Dinger oversaw the new study. "It is likely that the genomes of all cells in our body form i-motifs at certain points in time."

The results of the work are published in Nature Chemistry (Zeraati et al., I-motif DNA structures are formed in the nuclei of human cells).

The role of i-motives is not yet clear. Perhaps they help the body to control the "on" and "off" of certain genes, starting or stopping the synthesis of the corresponding proteins.

Four-core i-motifs are formed only on small sections of the genome, they form something like "nodules" on the surface of a smooth spiral structure that is familiar to us from school textbooks. Moreover, not every DNA fragment can "tie" into such a "knot" – this requires the presence of a special sequence of nucleotides.

I-motifs were discovered in the early 1990s, but the first experiments in this area showed that DNA is able to "tie a knot" only in an acidic environment. There can't be such a level of acidity inside a living cell, so the detection of i-motives aroused very moderate interest from doctors and biologists. The find was attributed to interesting unique phenomena and forgotten.

However, later studies have amended the theory. It turned out, for example, that i-motifs can be formed without the presence of acid, in situations when DNA becomes too "tight". Since the cell nucleus is a densely filled organoid, scientists have suggested that i–motifs are able to form in the natural environment.

By taking specific antibodies and modifying them so that they begin to fluoresce, the authors of the new study began searching for i-motifs (now highlighted) in the nucleus of a living cell. It turned out that the "nodules" are really present in it, though not constantly. The I-motifs were able to "tie" and "untie" depending on the acidity of the environment.

In addition, it turned out that "nodules" are usually formed not in the genes themselves, but on DNA sites called promoters. These sites are responsible for the activation of genes.

It is possible that i-motives can play the role of switches. For example, certain conditions change the acidity inside the cell, thereby stimulating the formation of a "nodule", which, in turn, starts or turns off the corresponding gene. However, it is not yet known how this switch works (when it is switched to the "on" state, and when it is "off"). Moreover, it is not known whether it works at all – it is likely that i-motifs do not actually play any role in controlling gene expression. More research will be needed to find out.

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