One enzyme sets the pace of your body clock
Your body clock ticks like a watch, but that watch only keeps time because one enzyme is in the right place. New findings reveal precisely how that works.
The circadian rhythm, the biological day-night cycle of cells, is driven by a feedback loop of proteins. Central to this loop are PER and CRY proteins, produced in the evening and broken down at night. That cycle sets the biological clock. But the timing of that breakdown depends heavily on an enzyme called CK1-delta. Researchers published new findings in the journal eLife on how this enzyme functions inside the cell nucleus.
The enzyme only works when it is bound
CK1-delta is unstable in the cell nucleus when free: it is rapidly broken down or actively exported. Only when it is bound to a PER protein does it remain long enough in the nucleus to function. The researchers showed that CK1-delta can break the connection between PER2 and CRY1 by phosphorylating PER2 (a chemical modification via a phosphate group). This releases CRY1, which then shifts back to the nucleus, where it suppresses clock activity.
This mechanism explains how the biological clock transitions smoothly from the early to the late repressive phase, a transition that was previously difficult to explain. PER2 accumulates in the cytosol of the cell during this phase, while CRY1 remains active in the nucleus.
What does this mean for aging and sleep?
As people age, the robustness of circadian rhythms declines. Sleep becomes less deep, and rhythms grow more irregular. If CK1-delta regulation deteriorates, the timing of the PER-CRY loop may shift. This study provides a mechanistic framework for that phenomenon, though the researchers themselves draw no conclusions about aging yet. That is a direction for future research. The findings do offer a concrete entry point for developing drugs that stabilise the body clock.