To learn faster, the brain constantly breaks its DNA.

DNA double-strand breaks are dangerous genetic damage, but they are very important in normal cellular processes. — Double-strand DNA breaks are dangerous genetic damage, but they are very important in normal cellular processes.

The brain reacts to threats quickly. It not only forms new neural connections, but also breaks the DNA of its cells, and then recreates the genome, accelerating the expression of the genes for learning and memory.

The discovery allows us to understand the nature of brain plasticity and shows that DNA breaking is an important part of normal cellular processes. In addition, it forces scientists to change their attitude towards aging, disease and genomic events: usually they were explained by unfortunate coincidences. For details, we invite you under the cut, while our flagship begins Data Science course…

Double-strand DNA breaks (when both strands of the spiral staircase break at the same place along the genome) are a dangerous type of genetic damage associated with cancer, neuronal degeneration and aging. Therefore, the discovery is even more surprising: it is more difficult for cells to repair these breaks than other DNA damage, because there is no whole “template” for re-connecting the strands.

The positive role of DNA breaks has been noticed for a long time. Including certain genes, they are involved and in the development of neurons, and in the process of genetic recombination of chromosomes during cell division, allowing DNA fragments to recombine and generate a diverse spectrum of antibodies in the developing immune system. Previously, these were all considered exceptions to the rule that double-strand breaks were accidental and undesirable.

Turning moment came in 2015 when, under the leadership Li-Hui Tsai A group of scientists investigated the accumulation of double-strand breaks in neurons associated with Alzheimer’s disease.

The study participants were surprised by the fact that stimulation of cultured neurons caused double-strand breaks in their DNA, the latter immediately increasing the expression of dozens of fast-acting genes that affect synaptic activity in learning and memory.

The double-strand breaks seemed to regulate the activity of genes important for neuronal function. Scientists theorized that the breaks release enzymes stuck along the coiled DNA fragments in order to quickly transcribe nearby genes. But the idea was met with great skepticism.

“People just find it hard to imagine that double-strand breaks can be physiologically important,” says Li-Hui Tsai.

These findings were developed v research a group of scientists led by a postdoctoral fellow at the University of Queensland Paul Marshall… This study showed that DNA break caused two waves of amplified gene transcription: the first – immediately, the second – a few hours later.

As an explanation, the scientists proposed a two-stage mechanism: when DNA breaks, enzyme molecules are released for transcription, and the place of break is marked with an epigenetic marker – a methyl group. At the beginning of the repair of damaged DNA, this mark is removed – the second round of transcription begins, where even more enzymes are released.

Here, the double-strand break is not just a trigger, Marshall said. Later, it becomes a regulatory marker that guides the mechanisms to the break. Something similar was demonstrated by further studies:

V one of these, double-strand breaks were associated not only with the formation of the memory of fear, but also with the memory itself.
V friend Cai and his colleagues’ study showed that this controversial mechanism of gene expression may be pervasive in the brain.

In the new, published On July 1, in a PLOS ONE study, instead of cultured neurons, a group led by Li-Hui Tsai studied the brain cells of live mice that had received an electric shock.

When the scientists localized the genes that underwent double-strand breaks in the prefrontal cortex and hippocampus of shock-affected mice, they found the breaks in about hundreds of genes. Many of them are involved in synaptic processes associated with memory.

It is also interesting that double-strand breaks were also found in the neurons of non-electrocuted mice. According to Timothy Jerome (not participating in the study, but working in a related direction), such breaks in the brain occur completely normal. That is, the DNA of the brain is constantly being torn apart – this is amazing.

To confirm the conclusion, the scientists observed double-strand breaks in glia – non-neuronal brain cells that regulate various genes – and found that glia are involved in the formation and storage of memories, and DNA break can be a regulatory mechanism in many other types of cells. broader than previously thought.

But, even if important gene expression for memory consolidation or for others cellular functions is risky. If double-strand breaks occur in the same locations without proper repair, genetic information is lost. Tsai said this type of gene regulation makes neurons vulnerable to genome damage, especially during aging and under neurotoxic conditions.

Have Bruce Yankner, a neuroscientist and geneticist at Harvard Medical School, is interested in the fact that such intense ruptures do not lead to destructive damage to brain cells.

The recovery process is likely to be effective, but effectiveness may decrease with age. Scientists are investigating the possibility of converting the breakdown mechanism into a mechanism of neuronal degeneration in conditions, for example, Alzheimer’s disease, as well as the effect of the mechanism on the development of glial tumors and post-traumatic stress.

If double-strand breaks regulate gene activity in cells outside the nervous system, the disruption of the mechanism can lead to muscle tissue atrophy or heart disease.

As the nuances of using the tearing mechanism are revealed, new therapeutic treatments for related diseases will be developed. Given the importance of double-strand breaks in basic memory processes, trying to prevent such breaks can be a mistake.

With the new discovery, it becomes necessary to think of the genome as a dynamic system. After breaking the sample [ДНК] changes – and, according to Paul Marshall, that’s not necessarily a bad thing.

Marshall’s group began research other types of DNA changes associated with deregulation and negative consequences, including cancer. According to him, many find it difficult to view DNA breaking as a fundamental mechanism for regulating gene transcription, researchers see DNA damage in this process. However, the new discovery and the results of Tsai’s work open the way for deeper research.

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