People with [delayed sleep phase disorder] are unable to fall asleep until late at night (often after 2 a.m.) and have difficulty getting up in the morning. In 2017, scientists discovered a surprisingly common mutation that causes this sleep disorder by altering a key component of the biological clock that maintains the body’s daily rhythms. The new findings… reveal the molecular mechanisms involved and point the way toward potential treatments.
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The mutation affects a protein called cryptochrome, one of four main clock proteins. Two of the clock proteins (CLOCK and BMAL1) form a complex that turns on the genes for the other two (period and cryptochrome), which then combine to repress the activity of the first pair, thus turning themselves off and starting the cycle again. This feedback loop is the central mechanism of the biological clock, driving daily fluctuations in gene activity and protein levels throughout the body.
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“The region that gets snipped out actually controls the activity of cryptochrome in a way that leads to a 24-hour clock,” [researcher Carrie] Partch explained.
“How tightly the complex partners bind to this pocket determines how quickly the clock runs,” Partch explained. “This tells us we should be looking for drugs that bind to that pocket and can serve the same purpose as the cryptochrome tail.”
