Circadian Rhythms

Keeping an Eye on the Clock

Science's STKE  17 Jan 2006:
Vol. 2006, Issue 318, pp. tw486
DOI: 10.1126/stke.3182006tw486

As part of the cycle of the intrinsic circadian clock, two proteins, PER and TIM, are thought to slowly associate in the cytoplasm of cells. This process takes 4 to 6 hours, after which the dimers enter the nucleus of the cell and interact with other clock components and close one of the clock's feedback loops. Meyer et al. (see the Perspective by Dunlap) labeled both PER and TIM in single living Drosophila cells with tags that emit a fluorescent signal when the proteins are in close proximity. The proteins did indeed associate with the expected time course, but, surprisingly, PER and TIM dissociated before moving to the nucleus. The extent of nuclear localization was independent of the concentrations of PER and TIM in the cytoplasm. Thus, fundamental assumptions about how the circadian clock keeps time need to be revisited.

P. Meyer, L. Saez, M. W. Young, PER-TIM interactions in living Drosophila cells: An interval timer for the circadian clock. Science 311, 226-229 (2006). [Abstract] [Full Text]

J. C. Dunlap, Running a clock requires quality time together. Science 311, 184-186 (2006). [Summary] [Full Text]