DNA Repairs Delays Age-Related Disease

In neurons, DNA damage may occur at any time and any genomic site. The DNA repairs would occur throughout the genome randomly. According to the new study by stalk scientists, some genomic sites are privileged. The scientist presented their article in Science on the topic of Incorporation of a nucleoside analogue maps genome repair sites in postmitotic human neurons.

The head of the line for repairs, these genomic sites are hot spots that play a critical role in neural identity and function. DNA Repair Hotspots may point to new therapies for diseases such as Alzheimer’s, Parkinson’s, and other age-related dementia disorders.The article showed that identifying DNA Repair Hotspots depends on looking for instances of repair, rather than performing the more usual activity, that is, looking for instances of damage. The Salk scientists had developed a new technique, Repair-seq.

The author wrote that to understand the genome integrity in neurons, we developed a sequencing method capable of capturing a genomic distribution of all DNA repair by the nonreplicative incorporation of the nucleoside analogue 5-ethynyl-2ʹ-deoxyuridine. The researchers collected the human embryonic stem cell-induced neurons that are postmitotic neurons to identity after the addition of doxycycline through NEUROG2 expression. The embryonic stem cell-induced neurons were labelled with EdU for 24 hours, and sites of DNA repair synthesis were identified by the enrichment of next-generation sequencing libraries containing EdU.

The authors found approximately 65,000 hot spots that covered around 2% of the neuronal genome using the Repair Seq technique. They used the proteomics method to find the kinds of protein found at those hotspots. Neurons don’t replace themselves over time. They are the longest living cells in the human body. Their life spans make it important that they repair lesions in their DNA as they age, to maintain their function over the decades of a human life span. neurons can make these genetic repairs decline, which could explain why people develop age-related neurodegenerative diseases like Alzheimer’s and Parkinson’s.