Cyanobacteria are the simplest organisms known to have a circadian clo
ck. A circadian crock gene cluster kaiABC was cloned from the cyanobac
terium Synechococcus. Nineteen clock mutations were mapped to the thre
e kai genes. Promoter activities upstream of the kaiA and kaiB genes s
howed circadian rhythms of expression, and both kaiA and kaiBC messeng
er RNAs displayed circadian cycling. inactivation of any single kai ge
ne abolished these rhythms and reduced kaiBC-promoter activity. Contin
uous kaiC overexpression repressed the kaiBC promoter, whereas kaiA ov
erexpression enhanced it. Temporal kaiC overexpression reset the phase
of the rhythms. Thus, a negative feedback control of kaiC expression
by KaiC generates a circadian oscillation in cyanobacteria, and KaiA s
ustains the oscillation by enhancing kaiC expression.