Light-Independent Role of CRY1 and CRY2 in the Mammalian Circadian Clock
Edmund A. Griffin Jr.,
David Staknis,
Charles
J. Weitz
*
Cryptochrome (CRY), a photoreceptor for the
circadian clock in Drosophila, binds to the clock component
TIM in a light-dependent fashion and blocks its function. In mammals,
genetic evidence suggests a role for CRYs within the clock, distinct
from hypothetical photoreceptor functions. Mammalian CRY1 and CRY2 are
here shown to act as light-independent inhibitors of CLOCK-BMAL1, the
activator driving Per1 transcription. CRY1 or CRY2 (or both)
showed light-independent interactions with CLOCK and BMAL1, as well as
with PER1, PER2, and TIM. Thus, mammalian CRYs act as light-independent
components of the circadian clock and probably regulate Per1
transcriptional cycling by contacting both the activator and its
feedback inhibitors.
Department of Neurobiology, Harvard Medical School, Boston,
MA 02115 USA.
*
To whom correspondence should be addressed. E-mail:
cweitz{at}hms.harvard.edu
