“Junk DNA” is a bit of a controversial term. Since as early as the 1960s, its been used describe the 98% of the genome that doesn’t code for proteins, and, while the name stuck, research over the past two decades has shown it’s far from dormant.
Now, researchers at the University of Sheffield have discovered that junk DNA, or non-coding DNA, also breaks—and, if it isn’t repaired, can contribute to the development of neurodegenerative disease. They hope their findings will lead to the identification of disease biomarkers along with new therapies.
“Until now the repair of what people thought is junk DNA has mostly been overlooked, but our study has shown it may have vital implications on the onset and progression of neurological disease,” Sherif El-Khamisy, chair in molecular medicine at the University of Sheffield and co-corresponding author, said in a press release.
Non-coding DNA had previously been implicated in neurological conditions via several different mechanisms, but the role of strand breaks and their repair is a new finding. According to the study, published Sept. 28 in Nature, the researchers showed that non-coding DNA acting as promoters—sequences where proteins bind to kick-start RNA transcription—were prone to strand breaks due to oxidative stress from cell metabolism.
Ideally, the promoters are repaired in a process mediated by nuclear mitotic apparatus protein NuMA, the study explained. But if NuMA is depleted, oxidative damage and strand breaks accumulate, leading to dysfunction and ultimately opening the door to Alzheimer’s disease, dementia, MND and other conditions.
“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,” El-Khamisy said. “By therapeutically targeting components of the pathway it may help us delay or treat neurological diseases such as dementia.”
The findings could also be applied to new cancer therapies. Variants in non-coding DNA have been linked to cancer development, and non-coding RNA, which is transcribed from non-coding DNA, is thought to play a role in cancer resistance.
Indeed, non-coding DNA has emerged as a target of interest in recent years as researchers uncover the secrets of the “junk” genome. Massachusetts-based Rome Therapeutics specifically studies the repeatome, or repetitive sequences of non-coding DNA, to find ways to treat cancer and autoimmune disease. And last year, Fierce reported that researchers from Washington University in St. Louis licensed out a drug that increases the expression of a non-coding RNA dubbed NXTAR, which suppressed prostate cancer development in mice.
Editor's note: A previous version of this article stated that the term "junk DNA" was coined in 1972. It has been updated to reflect that it has been in use since as early as the 1960s.