Nap for the biological clock

We can sleep for a while to regulate sleep circulation, but our cells have a much more subtle and delicate system. Humans, like most other organisms, have 24-hour rhythms controlled by a very precise molecular clock running inside each cell.

After decades of research, scientists are still trying to identify the mechanism of the circadian clock and put the machine's molecular gears in place. New research by Rockefeller University scientists shows the interaction mechanism of two of the critical molecules to control the circadian clock's cycle, as well as the turbulence mechanism. The type of physiological rotation, from which it is possible to identify the causes of genetic sleep disorders.

Michael Young, Richard and Jeanne Fisher, a professor and head of the genetics laboratory, and colleagues have shown that the biological clock carries an on-off switch controlled by an enzyme called doubletime. Doubletime, or DBT, has such a name because the gene mutation encodes enzymes that make the biological clock run like a fly. DBT works by attaching a phosphate group to proteins, a process called phosphorylation. The protein sequence that DBT phosphates, called period or PER, plays an important role in regulating the time of the biological clock, controlling the activity of other genes in the cycle of turning off and on. continuous hours. Scientists understand DBT's role in controlling the period protein by attaching a group of phosphates to this protein. But Young's new research shows that DBT can repress or activate PER by attaching phosphate groups to different locations.

The new study uncovers the mechanism of the circulatory disorder in the body clock to identify the causes of genetic sleep disorders. (Photo: iStockphoto / Phil Date )

The discovery that DBT has not one but two phosphate targets on PER shows that this enzyme acts as a switch."It's a phosphoric switch controlled by doubletime that determines whether or not the protein works," Young said . During the 'off' stage , the cell stimulates stable but inactive PER proteins, which are caused by phosphate groups in the first target position. During the 'on' stage , the phosphate group at the second target site activates the protein but destabilizes it so that PER is only active for a few hours. The cell then accumulates inactive proteins and the cycle begins.

Young and colleagues also found mutations in DBT that accelerated the biological clock: The period proteins that missed the first phosphorylation target had phosphorylation suppression when the switch 'turned on'. Therefore, the period protein is not completely stable. Young said: 'If you don't dissociate the first goal, you will automatically skip to the second goal, quickly diversify the second goal and create an outrageous restraint. When restraint works too soon and disappears quickly, you encounter a ' short cycle ' phenomenon . In other words, you wake up too early and go to bed too early, or you have a biological clock running fast.

Scientists have always studied families with members who have inherited the genetic version of this 'short-cycle' phenomenon, called FASPS (Family Early Sleep Syndrome). People with this syndrome wake up before dawn and go to sleep before sunset. Research on one of such families in Utah has shown a similar shortcoming in phosphorylation at the protein period. Researchers believe that the effects detected on flies, revealed by Young's team, could also be the cause of a fast-running biological clock in people with FASPS. Young said: 'Many of the characteristics found in humans are also consistent with what is found in flies. So it can also help us understand the syndrome that people have. '

Refer:
Kivimäe et al.Activating PER Repressor through a DBT-Directed Phosphorylation Switch.PLoS Biology, 2008;6 (7): e183 DOI: 10.1371 / journal.pbio.0060183