Those so-called "PAR-domain basic leucine zipper transcription factors" (PAR bZip) are known to accumulate in body tissues, including the liver and kidneys, in a highly circadian manner, the researchers said. Circadian refers to biological variations within a roughly 24 hour period.
The findings in mice underscore the crucial role of the body's daily timekeeping system in modulating drug toxicity, the researchers said, and suggest that patients might benefit from treatment regimens that are scheduled accordingly.
The findings also highlight the general importance of circadian clocks to many body functions, said Ueli Schibler of the University of Geneva.
"I think it's fair to say that nearly all physiology has some circadian component," Schibler said. "People think of jet lag as a sleep disturbance, when that may be the least of the problem," he added. "All of your organs--from the gastrointestinal system to liver enzymes, for example--depend on clocks."
Circadian rhythms control rest-activity cycles, heartbeat frequency, body temperature, blood pressure, hormones, and metabolism, among other behavioral and physiological processes.
The circadian timing system of mammals has a hierarchical structure, in that a master pacemaker in the brain synchronizes self-sustaining and cell-autonomous circadian clocks present in virtually all tissues, the researchers said. Drivers of circadian rhythms in peripheral cells--such as the three PAR bZip proteins: DBP, TEF, and HLF--mediate rhythmic physiology by regulating the activity of still other genes.