Control Mechanism of the Circadian Clock for Timing of Cell Division in Vivo

TLDR

Cell division in many mammalian tissues follows circadian timing, yet the mechanism by which the clock regulates this remains unclear. In regenerating mouse liver, the circadian clock directly regulates cell‑cycle gene expression—including Wee1—to modulate Cyclin B1‑Cdc2 activity, thereby unidirectionally controlling mitosis while remaining independent of the cell cycle in single cells.

Abstract

Cell division in many mammalian tissues is associated with specific times of day, but just how the circadian clock controls this timing has not been clear. Here, we show in the regenerating liver (of mice) that the circadian clock controls the expression of cell cycle–related genes that in turn modulate the expression of active Cyclin B1-Cdc2 kinase, a key regulator of mitosis. Among these genes, expression of wee1 was directly regulated by the molecular components of the circadian clockwork. In contrast, the circadian clockwork oscillated independently of the cell cycle in single cells. Thus, the intracellular circadian clockwork can control the cell-division cycle directly and unidirectionally in proliferating cells.