A new pathway involved in the breaking and repairing of noncoding DNA has been discovered, which may lead to new treatments for neurological diseases.
Oxidative damage to our DNA is a natural by-product of cellular metabolism and builds-up as we age. This damage occurs to the regions of our genome that encode proteins, and has been linked to the development of neurodegenerative diseases, such as dementia, Alzheimer's disease and motor neurone disease. In a new study by the University of Sheffield and published in Nature, researchers have discovered that this damage can also occur in the noncoding 'junk' regions of our DNA, including regions involved in regulation of gene expression. They identified one particular pathway, mediated by a protein called NuMA, through which the noncoding DNA breakages are repaired.
'The significance of repairing DNA breaks in the invisible non-coding genome will open up a whole new field of research, including new targets for therapeutic interventions and biomarkers.' said Professor Sherif El-Khamisy, senior author of the paper and co-founder and deputy director of the Healthy Lifespan Institute at the University of Sheffield.
In the study, the researchers depleted the NuMA protein in cells and then exposed the cells to oxidative stress. The cells without NuMA had more damage to their noncoding DNA in response to the oxidative stress compared to cells with NuMA expression intact.
The researchers also identified that NuMa regulated the expression of over 2000 genes that were increased following oxidative stress. Some of these genes were discovered to be involved in maintaining neurological function.
Furthermore, they found that NuMA bound to and promoted the activity of many components involved in the repair of single-strand breaks, which are the most common form of DNA damage and implicated in the maintenance of neurological function.
The researchers believe their findings could pave the way to the discovery of methods that may help prevent the onset or progression of neurological disorders. 'By therapeutically targeting components of the pathway, it may help us delay or treat neurological diseases such as dementia.' said Professor El-Kahmisy '… Until now the repair of what people thought is junk DNA has been mostly overlooked, but our study has shown it may have vital implications on the onset and progression of neurological disease.'
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