AJP - Cell Physiology, Vol 271, Issue 5 C1646-C1651, Copyright © 1996 by American Physiological Society
Evidence for a central role of transcription in the timing mechanism of a circadian clock
S. B. Khalsa, D. Whitmore, B. Bogart and G. D. Block
Department of Biology, University of Virginia, Charlottesville 22903, USA.
The retinal circadian clock in the isolated in vitro eye of the marine
mollusc Bulla gouldiana exhibits a phase-dependent requirement for
transcription. The transcription-sensitive phase extends through most of
the subjective day and therefore is substantially longer than the
previously reported translation-sensitive phase. Lower concentrations of
transcription inhibitors yield a significant dose-dependent lengthening of
circadian period. Clock motion can be stopped by a high concentration of
the transcription inhibitor 5,6-dichlorobenz-imidazole riboside (DRB) when
applied during the sensitive phase; after withdrawal of the inhibitor,
motion resumes from the phase at which it was stopped. In a double-pulse
experiment, phase shifts to light pulses applied after DRB pulses, and not
during the translation-sensitive phase, indicate that the inhibition of
transcription has immediate effects on the phase of the clock. These data
suggest that DRB-induced phase shifts are independent of translation, which
implies that the rate of transcription itself plays a significant role in
the mechanism underlying the generation of the circadian cycle.
