20 June 2023

Novosibirsk scientists found a way to combat DNA damage

Employees of the Institute of Chemical Biology and Fundamental Medicine SB RAS (Novosibirsk) discovered a new type of damage to the DNA molecule and found out how it can be repaired.
Body cells are constantly attacked by chemical and physical agents (radiation, ultraviolet radiation, hazardous chemicals, and even oxygen) that can kill or damage them. To protect the genome from such influences, there is a system of repair - that is, restoration - of DNA.

The most unwanted damage that leads to severe genetic diseases are AP sites (something like a broken DNA molecule). Scientists have known about them for a long time, but only recently has it become known that AP sites can form protein cross-links directly in a living cell. Due to their large size, the cross-links prevent cells from fully renewing themselves. Therefore, the body "invented" a repair system, which destroys the protein part of the cross-linkage, but after that the AP site with the peptide "tail" remains. And this is what happens to this fragment of the DNA molecule next, it was not clear.

The Novosibirsk scientists figured it out. They developed a way to produce cross-links of peptides with the AP site in DNA and used this model to study the mutagenic properties of such damage and methods of repair. They saw that the DNA fragment continues to be copied, which is how the mutation occurs. The study found that the same enzyme, AP endonuclease, works to destroy both protein cross-links and AP sites.

The scientists' findings will move the search for an effective remedy against DNA damage. The work of the researchers was funded by a grant from the Russian Science Foundation. The results were published in the prestigious international journal Nucleic Acids Research, the institute said.
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