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- Title
A PERIOD inhibitor buffer introduces a delay mechanism for CLK/CYC-activated transcription
- Authors
Weber, Frank; Kay, Steve A.
- Abstract
We investigated the functions of clock genes period (per) and timeless (tim) in establishing negative feedback on circadian transcription factors clock/cycle (Clk/cyc) in Drosophila. We show that PER protein persists for several hours after rapid degradation of TIM in the morning. We observed in cell culture that isolated PER inhibits CLK/CYC-activated transcription in the absence of TIM and we further demonstrated for the first time in vivo that PER accumulation in a tim loss-of-function mutant background causes efficient inhibition of CLK/CYC-dependent transcription. These results identify PER to be the main inhibitor for CLK/CYC and they suggest a delay mechanism during early morning, when PER protein, after degradation of TIM, forms an inhibitor buffer for CLK/CYC that attenuates the restart of the next cycle of CLK/CYC-activated transcription. While TIM likely enhances the inhibition of CLK/CYC by PER in the dark, our results suggest a reduction of PER-mediated inhibition by TIM in light.
- Subjects
GENES; CIRCADIAN rhythms; TRANSCRIPTION factors; PROTEINS
- Publication
FEBS Letters, 2003, Vol 555, Issue 2, p341
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/S0014-5793(03)01269-9