Telomeres and radicals

Oxygen was set on telomeric DNA

Thus, scientists have confirmed that it causes chromosome shortening and cell aging

Polina Loseva, "The Attic"

One of the main causes of cellular aging is the loss of the end sections of chromosomes – telomeres. This can happen for a variety of reasons, including under the action of reactive oxygen species under oxidative stress. Since this process develops throughout the cell at the same time, it is difficult to understand to what extent it affects the telomeres. Researchers from Pittsburgh have developed a way to target the ends of chromosomes with free radicals. As a result of a prolonged attack, the telomeres in the cells began to "deteriorate", the chromosomes began to stick together, and the attempts of the cells to multiply ended in death.

Article by Fouquerel et al. Targeted and Persistent 8-Oxoguanine Base Damage at Telomeres Promotes Telomere Loss and Crisis is published in the journal Molecular Cell.

Telomeres are areas at the ends of chromosomes consisting of many "meaningless" repeats. Their main role is to protect the "significant" parts of DNA that carry genetic information. In particular, during cell division, chromosomes inevitably shorten, due to the fact that their ends cannot be completely copied. Telomeres take the hit and lose several repetitions from their set each time. Thanks to this, the basic DNA remains intact.

When telomeres become extremely short, the cell stops dividing. This phenomenon is called replicative aging. It involves a complex of proteins called shelterins. Normally, they are associated with telomeric DNA, but as it becomes shorter, they do not have enough space, telomeres enter the cytoplasm of the cell and block its reproduction.

At the same time, telomeres can disappear not only during cell division. It is believed that other factors may be involved in this, for example, oxidative stress – the accumulation of reactive oxygen species in the cell, which destroy cellular macromolecules. However, it is quite difficult to find out whether they affect telomeres directly or act through some side mechanisms, because stress develops in all parts of the cell. American researchers have come up with a way to "incite" free radicals directly on telomeres.

To do this, they attached a photosensitive dye to one of the shelterins. Under the action of light with a certain wavelength, the dye separates a singlet oxygen molecule from itself. But since the dye was concentrated near the telomeres, when it is activated, oxidative stress does not occur throughout the cell, but only in a small part of the nucleus.

The scientists tested this system on a culture of HeLa tumor cells. It turned out that under the influence of singlet oxygen, a lot of damage occurred in telomeric DNA – extra oxygen atoms appeared in guanine nucleotides. A one-time attack did not greatly affect the life of the cells: special enzymes began to work in them, which replaced the damaged nucleotides.

But if singlet oxygen acted on the cells for a long time, then there was so much damage that the cell could not cope with repairing telomeres and removed problem areas. Telomeres became shorter and disappeared over time. As a result, the ends of the chromosomes were "bared" and stuck together, forming interchromosomal bridges.

At the same time, the cells could not multiply, and attempts to divide into two parts led to their death. Thus, oxidative stress can directly accelerate the aging of DNA and, consequently, the entire cell as a whole.

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