New sleep study suggests DNA repair protein tells us we’re tired

By Michael IrvingNovember 22, 2021

A new study sheds new light on why almost all organisms need sleep

A new study sheds new light on why almost all organisms need sleepevgenyataman/DepositphotosVIEW 1 IMAGES

Birds do it. Bees do it. Anything with even a rudimentary nervous system does it. Sleep is a crucial biological phase, but exactly why we need it remains mysterious. Now a study has uncovered a new piece of the puzzle, finding that a protein involved in DNA repair signals the brain when it’s time to sleep.

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.


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But what is the actual mechanism behind that pressure? In previous work, researchers at Bar-Ilan University 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 more 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 researchers went on to investigate the role of PARP1 in mice, and sure enough inhibiting its activity reduced the duration and quality of their sleep. While PARP1 is known to have a DNA repair role in humans, future work will need to be conducted to investigate whether this mechanism applies to humans too.

The research was published in the journal Molecular Cell.

Source: Bar-Ilan University

We recommend

  1. Sleeping Helps Clearing the DNA Damaged While You are AwakeEnago Academy, 2019
  2. A moderate increase in dietary zinc reduces DNA strand breaks in leukocytes and alters plasma proteins without changing plasma zinc concentrationsZyba et al., The American Journal of Clinical Nutrition, 2016
  3. Effect of Human XRCC1 Protein Oxidation on the Functional Activity of Its Complexes with the Key Enzymes of DNA Base Excision RepairI. A. Vasil’eva et al., Biochemistry (Moscow), 2020
  1. Light-induced modulation of DNA recognition by the Rad4/XPC damage sensor proteinAmirrasoul Tavakoli et al., RSC Chemical Biology, 2021
  2. Interactome of Base and Nucleotide Excision DNA Repair SystemsN. I. Rechkunova et al., Molecular Biology, 2021
  3. Protein–DNA interactions in high speed AFM: single molecule diffusion analysis of human RAD54Sanchez et al., Integrative Biology

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