20 September 2022

DNA packaging is the key to longevity

Telomeres are the end sections of DNA that many researchers consider to be the key to longevity. They protect the genes from damage, but after each division, the cells shorten. If the telomere length becomes too small, the cell dies.

John van Noort of the Leiden Institute of Physics has discovered a new DNA packaging scheme. As a biophysicist, he used the laws of physics for biological experiments. Together with biologists from Nanyang Technological University in Singapore, van Noort studied the structure of DNA telomeres.

In every cell of the human body there are chromosomes carrying genes that determine the characteristics of the organism. At the ends of the chromosomes are telomeres that protect them from damage. They look like tips on shoelaces.

The DNA strand has an average length of two meters; to fit in the cell, it is in a twisted state. This is achieved by wrapping DNA around histone proteins; a complex of DNA and proteins is called a nucleosome. It turns out a string of beads: a nucleosome-bead alternates with a fragment of free DNA, then again a nucleosome-bead, and so on.

These beads, in turn, are also twisted, depending on the length of the DNA strand between the nucleosomes. Two types of DNA twisting are already known: in the first of them, two neighboring nucleosomes stick together, and a free DNA strand hangs between them (Fig. A). If the free DNA between the beads is shorter, the neighboring beads do not have time to stick together, and two columns are formed next to each other (B).

dna-structure.jpg

In the new study, Van Noort and his colleagues discovered another DNA structure: the nucleosomes are located much closer to each other, so there is simply no free DNA between them. It turns out one large DNA helix (C).

The new structure was discovered using a combination of electron microscopy and molecular spectroscopy. The researchers fixed one end of the DNA on a slide, and attached a magnetic ball to the other. Then, by the influence of strong magnets on this ball, they straightened the DNA strand. By measuring the force needed to untangle the DNA beads one by one, the researchers obtained information about how the thread is folded.

Knowing the structure of DNA gives an understanding of how genes turn on and off and how enzymes in cells affect telomeres: for example, how they repair and copy DNA. And this, in turn, will help to study aging and age-related diseases, including cancer, and develop drugs to combat them.

Article by A.Soman et al. Columnar structure of human telomeric chromatin is published in the journal Nature.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of Leiden University: Can we live longer? Leiden physicist makes discovery in protective layer in genes.


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