Neuronal Enhancers Identified as Hotspots for DNA Single-Strand Break Repair

Researchers at the National Institutes of Health have discovered specific regions within the DNA of neurons that accumulate single-strand breaks (SSBs) damage. Their findings were published in Nature. 

Because neurons require considerable amounts of oxygen to function properly, they are exposed to high levels of free radicals. Normally, this damage occurs randomly. However, in this study, damage within neurons was often found within specific regions of DNA called enhancers that control the activity of nearby genes. Closer inspection of the neurons revealed that a significant number of SSBs occurred when methyl groups were removed, which typically makes that gene available to be activated.

An explanation proposed by the researchers is that the removal of the methyl group from DNA itself creates an SSB, and neurons have multiple repair mechanisms ready to repair that damage as soon as it occurs. This challenges the common wisdom that DNA damage is inherently a process to be prevented. Instead, at least in neurons, it is part of the normal process of switching genes on and off. Furthermore, it implies that defects in the repair process, not the DNA damage itself, can potentially lead to developmental or neurodegenerative diseases.

The team is now looking more closely at the repair mechanisms involved in reversing neuronal SSBs and the potential connection to neuronal dysfunction and degeneration.