Face a Threatened, the brain needs to work faster, its neurons are making new connections to know what the difference between life and death might be. But in response, the brain also increases scarring: a recent discovery shows that in order to speed up the development of learning and memory genes, brain cells disintegrate their DNA at many important points, and then rebuild their broken genomes.
The search does not simply provide insights into the nature of the plasticity of the brain. This further proves that DNA breakdown can be a routine and important part of the normal cellular process – which has implications for how scientists think about aging and disease and how they approach genomic events they usually write off as unfortunate.
The discovery is even more surprising because the DNA double-strand break, where both rails of the helical ladder along the genome are cut in the same position, is a particularly dangerous type of genetic damage associated with cancer, neurodegeneration and aging. Double-strand breaks are more difficult for cells to repair than other types of DNA damage because there is no intact “template” left for the strands to reconnect.
Yet it has long been recognized that DNA breakdown sometimes plays a constructive role. When cells divide, double-strand breaks allow the normal process of genetic reorganization between chromosomes. In the developing immune system, they are able to replicate DNA fragments and create a diverse collection of antibodies. Double-strand breaks are also involved to help with neuronal development and the introduction of specific genes. Nevertheless, these actions seem to be the exception to the rule that double-strand breaks are accidental and unintended.
But in 2015 a turning point came. New-scientist and director Li-Hui Sai, director of the Pickwear Institute for Learning and Memory at the Massachusetts Institute of Technology, and his colleagues were following previous work that linked Alzheimer’s disease to deposits. Double strand break in neurons. To their surprise, the researchers found that stimulated cultured neurons initiated double-strand breaks in their DNA and that breaks enhanced the expression of a dozen fast-acting genes associated with rapid learning and synaptic activity in memory.
Double-strand breaks seemed essential for controlling gene activity, which is important for neuron activity. Tsai and his colleagues speculated that fragments of DNA break down vitally secreted enzymes, freeing them to quickly replicate relevant genes around them. But the idea “came with a lot of skepticism,” Tsai said. “It’s just hard for humans to imagine that a double-strand break could actually be physiologically important.”
Nevertheless, Paul Marshall, a postdoctoral researcher at the University of Queensland in Australia, and his colleagues decided to follow this research. Their work, which was published in 2019, has both confirmed and expanded the observation by Tsai’s team. It showed that DNA breakdown reached two waves of advanced gene transcription, one instantaneous and a few hours later.
Marshall and his colleagues proposed a two-step process to explain the phenomenon: when DNA breaks down, some enzyme molecules are released for transcription (as the Cyr group suggests) and the break point is also chemically flagged with the methyl group, hence-called epigenetic markers. Later, when the repair of the broken DNA begins, the marker is removed – and in the process, more enzymes can be released, which initiates the second round of replacement.
“Not only double-strand brakes are involved as triggers,” Marshall said, “it then became a marker and the marker itself is effective in controlling and guiding equipment in that space. “
Since then, other studies have demonstrated something similar. A, published last year, double-strand break is not just associated with the formation of a fear memory, but also with its memory.
Now, in a study last month Plus one, Tsai and colleagues have shown that this reverse process of gene expression may be prevalent in the brain. This time, instead of using Sanskrit neurons, they looked at the brain cells of living rats that were learning to associate an environment with electric shock. When the team mapped double-stranded brake genes in the frontal cortex and hippocampus that were stunned, they found breaks near hundreds of genes, many of which were involved in memory-related synaptic processes.