Circadian expression of clock genes in human oral mucosa and skin Association with specific cell-cycle phases

We studied the relative RNA expression of clock genes throughout one 24-hou r period in biopsies obtained from the oral mucosa and skin from eight heal thy diurnally active male study participants. We found that the human clock genes hClock, hTim, hPer1, hCry1, and hBmal1 are expressed in oral mucosa and skin, with a circadian profile consistent with that found in the suprac hiasmatic nuclei and the peripheral tissues of rodents. hPer1, hCry1, and h Bmal1 have a rhythmic expression peaking early in the morning, in late afte rnoon, and at night, respectively, whereas hClock and hTim are not rhythmic , This is the first human study to show a circadian profile of expression f or all five clock genes as documented in rodents, suggesting their function al importance Fn man. In concurrent oral mucosa biopsies, thymidylate synth ase enzyme activity, a marker for DNA synthesis, had a circadian variation with peak activity in early afternoon, coinciding with the timing of S phas e in our previous study on cell-cycle timing in human oral mucosa, The majo r peak in hPer1 expression occurs at the same time of day as the peak in G( 1) phase in oral mucosa, suggesting a possible link between the circadian c lock and the mammalian cell cycle.