Sayak Banerjee, Amity University Kolkata
Many people have a wrong conception that since DNA damage can occur any time at any genomic site of a neuron, DNA repairs take place throughout the genome arbitrarily. Salk scientists have proved this view to be invalid saying that genomic sites are benefitted. Genomic sites are also known as “hotspots” are observed to have a vital role in the identification of neurons and their function. These DNA repair hotspots (DRH) are linked with age-related dementia and other neurodegenerative disorders like Alzheimer’s and Parkinson’s disease and their therapies.
In the article, the scientists have stressed the detection of DRH being dependent upon the cases of repair rather than the cases of damage. With the help of Repair-seq, they have discovered around 65,000 hotspots extending over 2% of the genome of the neuron. A lot of DRHs seemed to be relatively stable on treating with DNA damaging agents, and most of them were strongly connected with the epigenetic clock. Neurons are the longest living cells of the human body as they do not replace themselves over time, unlike other cells. This longevity is essential for them to maintain their function and repairing lesions over decades of a human life span. As they age the genetic repair ability decreases, due to which age-related neurodegenerative diseases take place.
Hotspots are filled with histone H2A isoforms and RNA binding proteins and are connected with evolutionarily preserved elements of the human genome. The scientists applied proteomics for the detection of several splicing-related proteins and they discovered that these proteins were involved in neurodegenerative diseases and sites associated with ageing. They mentioned that this is the first time research has exhibited the existence of certain portions of the genome which are more preferred by the neurons during the repair. These findings give us insights regarding additional methods that are needed for the study of genome integrity linked to ageing and disease and that Repair-seq will be a powerful research tool.
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