New research led by scientists at the University of Sheffield’s Neuroscience and Healthy Life Span Institutes demonstrates that oxidative breaks form and are repaired in “junk” DNA. The findings may lead to the development of therapeutic treatments for neurological disorders such as dementia, and Alzheimer’s disease, and may have implications for future cancer treatments.
The findings are published in the journal Nature in a paper titled, “A mechanism for oxidative damage repair at gene regulatory elements.”
“Oxidative genome damage is an unavoidable consequence of cellular metabolism,” wrote the researchers. “It arises at gene regulatory elements by epigenetic demethylation during transcriptional activation. Here we show that promoters are protected from oxidative damage via a process mediated by the nuclear mitotic apparatus protein NuMA (also known as NUMA1). NuMA exhibits genomic occupancy approximately 100 bp around transcription start sites. It binds the initiating form of RNA polymerase”
Until now, the repair of junk DNA has been overlooked by scientists, but the new study demonstrates it is much more vulnerable to breaks from oxidative genomic damage than previously thought.
Sherif El-Khamisy, PhD, professor, chair in molecular medicine at the University of Sheffield, and co-founder and deputy director of the Healthy Lifespan Institute, said: “The significance of repairing DNA breaks in the invisible noncoding genome will open up a whole new field of research, including new targets for therapeutic interventions and biomarkers. By therapeutically targeting components of the pathway, it may help us delay or treat neurological diseases such as dementia.”
Ilaria Bellantuono, PhD, professor and co-director of the Healthy Lifespan Institute at the University of Sheffield, said: “This work is important as it paves the way towards being able to identify new drugs to prevent the development of multiple diseases simultaneously and boost resilience in older people.”
