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"Alarm clock" gene explains wake-up function of biological clock

Luciano DiTacchio and Satchidananda Panda

Luciano DiTacchio and Satchidananda Panda

Ever wondered why you wake up in the morning, even without an alarm clock? Wonder no more. Researchers in the lab of Satchidananda Panda have identified a new component of the biological clock, a gene responsible for starting the clock from its restful state every morning.

The biological clock ramps up our metabolism early each day, initiating important physiological functions that tell our bodies that it's time to rise and shine. Discovery of this new gene and the mechanism by which it starts the clock every day may help explain the genetic underpinnings of sleeplessness, aging and chronic illnesses, such as cancer and diabetes, and could eventually lead to new therapies for these illnesses.

In a report published in Science, the Salk researchers and their collaborators at McGill University and Albert Einstein College of Medicine described how the gene KDM5A encodes a protein, JARID1a, which serves as an activation switch in the biochemical circuit that maintains our circadian rhythm. The discovery fills in a missing link in the molecular mechanisms that control our daily wake-sleep cycle.

In their research, Panda and his colleagues identified JARID1a, a type of enzyme, as the molecular bugle call for cells and organs to get back to work each morning. By studying the genetic mechanisms underlying circadian rhythms in human and mouse cells and in fruit flies, the researchers discovered that JARID1a was required for normal cycling, both at the cellular level and in terms of an organism's daily behavior.

Now that scientists understand why we wake each day, they can explore the role of JARID1a in sleep disorders and chronic diseases, possibly using it as a target for new drugs.

"So much of what it means to be healthy and youthful comes down to a good night's sleep," Panda says. "Now that we have identified JARID1a in activating our daytime cycle, we have a whole new avenue to explore why some people's circadian rhythms are off and to perhaps find new ways to help them."