How brain cells repair their DNA reveals “hot spots” of aging and disease

Good news! Possibly a breakthrough! This is probably some critical research!

"... Now, a new study by Salk scientists finds that these repairs are not random, but instead focus on protecting certain genetic “hot spots” that appear to play a critical role in neural identity and function. ...
“This research shows for the first time that there are sections of genome that neurons prioritize when it comes to repair,” ... “We’re excited about the potential of these findings to change the way we view many age-related diseases of the nervous system and potentially explore DNA repair as a therapeutic approach.” ...
The authors found approximately 65,000 hot spots that covered around 2 percent of the neuronal genome. They then used proteomics approaches to detect what proteins were found at these hot spots ...
Previous research has focused on identifying the sections of DNA that suffer genetic damage, but this is the first time researchers have looked for where the genome is being heavily repaired. ..."

"Humans have only a limited capacity to generate new neurons. These cells thus need to repair errors in the genome. To better understand this process, [researchers] developed Repair-seq, a method to locate DNA repair within the genome of stem cell–derived neurons. DNA repair hotspots (DRHs) were more likely to occur within specific genomic features such as gene bodies as well as in genomic formations, open chromatin, and active regulatory regions. This method showed that repair was enriched at sites involved in neuronal function and identity. Furthermore, proteomic data indicated that genes in DRHs are enriched in Alzheimer's disease and that DRHs are more active in aging. ..."

"Neurons are the longest-lived cells in our bodies and lack DNA replication, which makes them reliant on a limited repertoire of DNA repair mechanisms to maintain genome fidelity. These repair mechanisms decline with age, but we have limited knowledge of how genome instability emerges and what strategies neurons and other long-lived cells may have evolved to protect their genomes over the human life span. A targeted sequencing approach in human embryonic stem cell–induced neurons shows that, in neurons, DNA repair is enriched at well-defined hotspots that protect essential genes. These hotspots are enriched with histone H2A isoforms and RNA binding proteins and are associated with evolutionarily conserved elements of the human genome. These findings provide a basis for understanding genome integrity as it relates to aging and disease in the nervous system."

How brain cells repair their DNA reveals “hot spots” of aging and disease - Salk Institute for Biological Studies Salk scientists reveal new insights into neurodegenerative disorders and potential for genetic therapies

Here is the link to the underlying research article:

Incorporation of a nucleoside analog maps genome repair sites in postmitotic human neurons (no public access)