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Hot Spot For DNA Damage In Neurons Have Been Discovered

by Karishma Abhishek on March 29, 2021 at 8:59 AM

Specific regions within the DNA of neurons that accumulate a certain type of damage (called single-strand breaks or SSBs) have been discovered by the researchers at the National Institutes of Health (NIH).


The general understanding of the cause of DNA damage and its potential implications in neurodegenerative diseases is challenged by the accumulation of SSBs that appears to be unique to neurons.

‘Specific regions within the DNA of neurons that accumulate a certain type of damage (called single-strand breaks or SSBs) have been discovered. Further exploration of the repair mechanisms involved in reversing neuronal SSBs and the potential connection to neuronal dysfunction and degeneration may help in a better understanding of neurological diseases. ’

Neurons have high demand of oxygen to function properly and this exposes them to high levels of free radicals (toxic compounds that can damage DNA within cells). Generally, this damage occurs randomly.

But the present study shows the damage occurs within neurons in a specific region of DNA called "enhancers" that control the activity of nearby genes. Not all the genes are needed to be active at a given time in fully mature cells like neurons.

DNA Damage "Hot Spots"

One way that cells can control gene activity involves the presence or absence of a chemical tag called a methyl group on a specific building block of DNA. A significant number of SSBs was shown to occur when methyl groups were removed, which typically makes that gene available to be activated.

The present study laid the fact that the removal of the methyl group from DNA itself creates an SSB, and neurons have multiple repair mechanisms at the ready to repair that damage as soon as it occurs.

The common wisdom that DNA damage is inherently a process to be prevented is thus challenged here. It is part of the normal process of switching genes on and off at least in neurons. Furthermore, it implies that defects in the repair process, not the DNA damage itself, can potentially lead to developmental or neurodegenerative diseases.

Thus the study team successfully developed a method for mapping DNA errors within the genome that is highly sensitive. This technique requires a considerable number of cells to work effectively.

The team further seeks to explore the repair mechanisms involved in reversing neuronal SSBs and the potential connection to neuronal dysfunction and degeneration.

Source: Medindia

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