Metavalent Stigmergy

How New Default Consensus Realities Instantiate

Incorporation of a nucleoside analog maps genome repair sites in postmitotic human neurons

Nothing we’ve mentioned means mRNA engineering is obsolete! Far from it. Only means to maybe also pay attention to environmental factors & effects in the emergence of mutations and new strains. Does it make sense? Or no?

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DNA repair within neurons

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, Reid et al. 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. These observations link neuronal DNA repair to aging and neurodegeneration.

Abstract

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.

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CREDIT: @CedricBardyLab

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Written on April 1, 2021


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