Sleep Study Says DNA Repair Protein Tells Us When We're Tired

Everyone is familiar with the daily cycle. You wake up feeling refreshed (assuming you had a decent night’s sleep), then as the day goes on, tiredness builds up until you simply can’t do anything else but sleep. And the longer you stay up, the stronger that need becomes. This tiredness is more technically known as homeostatic sleep pressure, Michael Irving reported for New Atlas.

Photo Insert: Researchers found that tiredness - or homeostatic sleep pressure, involves DNA damage in neurons.

But what is the actual mechanism behind that pressure? In previous work, researchers at Bar-Ilan University in Israel found that it involves DNA damage in neurons. This damage can occur from normal biological processes, as well as environmental factors like UV light or radiation.

The body’s repair mechanisms are constantly working to fix the damage, but they can’t do it fast enough while the brain is awake. Their only chance to catch up is during sleep – a process that the team likens to workers fixing potholes in the road at night, when there’s less traffic.

For the new study, the researchers examined this process closely to find out if DNA damage to neurons directly drives homeostatic pressure. The team investigated using zebrafish, which have a similar brain to ours, only simpler.

They induced DNA damage in the animals’ neurons using chemicals, radiation, and light, and sure enough, when the damage reached a certain point, the fish would go to sleep.

Higher activity of DNA-repairing proteins were detected while the fish slept, and the team found that if they were woken up early – before they’d had six hours sleep – the DNA damage stuck around, and the animals were more likely to continue sleeping during daylight hours.

But the most intriguing find was a new role for a protein called PARP1. It’s already known to be a key player in the DNA repair system, responding to damage quickly and regulating other components that fix it. As such, PARP1 levels tend to increase during the day and decrease during sleep.

To check whether PARP1 is actively signaling the brain to sleep, the researchers overexpressed the protein in zebrafish, and found that it promoted sleep and DNA repair. The opposite also held true – when the team inhibited PARP1, the fish wouldn’t go to sleep and DNA repair didn’t occur. The research was published in the journal Molecular Cell.

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