Evidence for a central role of transcription in the timing mechanism of a circadian clock. Khalsa, Sat Bir S., David Whitmore, Barbara Bogart, and Gene D. Block. NSF Center for Biological Timing, Department of Biology, Gilmer Hall, University of Virginia, Charlottesville, VA 22903
APStracts 3:0198C, 1996.
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 -dichlorobenzimidazole riboside (DRB) when applied during the sensitive phase; following 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.

Received 26 February 1996; accepted in final form 30 May 1996.
APS Manuscript Number C104-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 July 96