Circadian clocks go in vitro : purely post-translational oscillators in cyanobacteria

Recent findings about the core of the circadian oscillator in cyanobacteria are challenging the dogma that such clocks are driven through transcriptional–translational feedback regulation. Instead, the master pacemaker is independent of both transcription and translation, and consists of self‐sustained oscillations in the phosphorylation status of the KaiC protein in vivo. Using a minimal cocktail of three recombinant proteins with adenosine triphosphate, the core clock was even reproduced in vitro. The so‐born chemical oscillator could reproduce accurately temperature compensation and altered period phenotypes in mutants. This system now provides an ideal playground for rebuilding the circadian clock by adding successive components while understanding every single step with chemical resolution.

[1]  Steven A. Brown,et al.  PERIOD1-Associated Proteins Modulate the Negative Limb of the Mammalian Circadian Oscillator , 2005, Science.

[2]  Tetsuya Mori,et al.  Circadian clock‐protein expression in cyanobacteria: rhythms and phase setting , 2000, The EMBO journal.

[3]  Tetsuya Mori,et al.  Circadian clock protein KaiC forms ATP-dependent hexameric rings and binds DNA , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Ook Joon Yoo,et al.  PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[5]  J. Hopfield,et al.  From molecular to modular cell biology , 1999, Nature.

[6]  D. Whitmore,et al.  Imaging of single light-responsive clock cells reveals fluctuating free-running periods , 2005, Nature Cell Biology.

[7]  Jimin Wang,et al.  Recent cyanobacterial Kai protein structures suggest a rotary clock. , 2005, Structure.

[8]  Paolo Sassone-Corsi,et al.  Zebrafish Clock rhythmic expression reveals independent peripheral circadian oscillators , 1998, Nature Neuroscience.

[9]  Tianfu Wu,et al.  NMR structure of the KaiC-interacting C-terminal domain of KaiA, a circadian clock protein: implications for KaiA-KaiC interaction. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[10]  T. Kondo,et al.  Reconstitution of Circadian Oscillation of Cyanobacterial KaiC Phosphorylation in Vitro , 2005, Science.

[11]  P. Tresco,et al.  A diffusible coupling signal from the transplanted suprachiasmatic nucleus controlling circadian locomotor rhythms , 1996, Nature.

[12]  M. Elowitz,et al.  A synthetic oscillatory network of transcriptional regulators , 2000, Nature.

[13]  A. Goldbeter,et al.  Toward a detailed computational model for the mammalian circadian clock , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[14]  P. Hardin,et al.  Drosophila CLOCK Protein Is under Posttranscriptional Control and Influences Light-Induced Activity , 2002, Neuron.

[15]  Michael W. Young,et al.  vrille, Pdp1, and dClock Form a Second Feedback Loop in the Drosophila Circadian Clock , 2003, Cell.

[16]  Stanislas Leibler,et al.  Resilient circadian oscillator revealed in individual cyanobacteria , 2004, Nature.

[17]  A. Winfree Biological rhythms and the behavior of populations of coupled oscillators. , 1967, Journal of theoretical biology.

[18]  Takao Kondo,et al.  No Transcription-Translation Feedback in Circadian Rhythm of KaiC Phosphorylation , 2005, Science.

[19]  S. Yamaguchi,et al.  Synchronization of Cellular Clocks in the Suprachiasmatic Nucleus , 2003, Science.

[20]  Eviatar Nevo,et al.  Origin and evolution of circadian clock genes in prokaryotes , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[21]  A. Ninfa,et al.  Development of Genetic Circuitry Exhibiting Toggle Switch or Oscillatory Behavior in Escherichia coli , 2003, Cell.

[22]  Jared Rutter,et al.  Regulation of Clock and NPAS2 DNA Binding by the Redox State of NAD Cofactors , 2001, Science.

[23]  S. Leibler,et al.  Mechanisms of noise-resistance in genetic oscillators , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[24]  Steven A. Brown,et al.  Peripheral Circadian Oscillators in Mammals: Time and Food , 2003, Journal of biological rhythms.

[25]  Steven H. Strogatz,et al.  Nonlinear Dynamics and Chaos , 2024 .

[26]  P. Hardin Transcription Regulation within the Circadian Clock: The E-box and Beyond , 2004, Journal of biological rhythms.

[27]  M. W. Young,et al.  Light-Induced Degradation of TIMELESS and Entrainment of the Drosophila Circadian Clock , 1996, Science.

[28]  C. Thummel,et al.  Faculty Opinions recommendation of Circadian gene expression in individual fibroblasts: cell-autonomous and self-sustained oscillators pass time to daughter cells. , 2004 .

[29]  U. Schibler,et al.  A Serum Shock Induces Circadian Gene Expression in Mammalian Tissue Culture Cells , 1998, Cell.

[30]  S. Golden,et al.  Resonating circadian clocks enhance fitness in cyanobacteria. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[31]  A. Sehgal,et al.  Role of Molecular Oscillations in Generating Behavioral Rhythms in Drosophila , 2001, Neuron.

[32]  M. W. Young,et al.  A Role for the Segment Polarity Gene shaggy/GSK-3 in the Drosophila Circadian Clock , 2001, Cell.

[33]  Paul E. Brown,et al.  Extension of a genetic network model by iterative experimentation and mathematical analysis , 2005, Molecular systems biology.

[34]  M. W. Young,et al.  double-time Is a Novel Drosophila Clock Gene that Regulates PERIOD Protein Accumulation , 1998, Cell.

[35]  Carl Hirschie Johnson,et al.  The Adaptive Value of Circadian Clocks An Experimental Assessment in Cyanobacteria , 2004, Current Biology.

[36]  Takao Kondo,et al.  Circadian Formation of Clock Protein Complexes by KaiA, KaiB, KaiC, and SasA in Cyanobacteria* , 2003, The Journal of Biological Chemistry.

[37]  S. Reppert,et al.  Coordination of circadian timing in mammals , 2002, Nature.

[38]  C. Johnson,et al.  Expression of a gene cluster kaiABC as a circadian feedback process in cyanobacteria. , 1998, Science.

[39]  S. Golden,et al.  Circadian Rhythms in Rapidly Dividing Cyanobacteria , 1997, Science.

[40]  Steve A. Kay,et al.  Bioluminescence Imaging of Individual Fibroblasts Reveals Persistent, Independently Phased Circadian Rhythms of Clock Gene Expression , 2004, Current Biology.

[41]  Takao Kondo,et al.  KaiA-stimulated KaiC phosphorylation in circadian timing loops in cyanobacteria , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[42]  Jan Pieter Abrahams,et al.  Structure at 2.8 Â resolution of F1-ATPase from bovine heart mitochondria , 1994, Nature.

[43]  C. R. McClung,et al.  The Arabidopsis thaliana Clock , 2004, Journal of biological rhythms.

[44]  Atsushi Hijikata,et al.  Role of KaiC phosphorylation in the circadian clock system of Synechococcus elongatus PCC 7942. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[45]  Jay C Dunlap,et al.  The Neurospora Circadian System , 2004, Journal of biological rhythms.

[46]  Felix Naef,et al.  Cellular oscillators: rhythmic gene expression and metabolism. , 2005, Current opinion in cell biology.

[47]  T. Kondo,et al.  Nucleotide binding and autophosphorylation of the clock protein KaiC as a circadian timing process of cyanobacteria. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[48]  J. Lieb,et al.  Sex-Specific Assembly of a Dosage Compensation Complex on the Nematode X Chromosome , 1996, Science.

[49]  Tetsuya Mori,et al.  Cyanobacterial circadian clockwork: roles of KaiA, KaiB and the kaiBC promoter in regulating KaiC , 2003, The EMBO journal.

[50]  S. Kay,et al.  Time zones: a comparative genetics of circadian clocks , 2001, Nature Reviews Genetics.

[51]  U. Alon Biological Networks: The Tinkerer as an Engineer , 2003, Science.

[52]  Takao Kondo,et al.  KaiB functions as an attenuator of KaiC phosphorylation in the cyanobacterial circadian clock system , 2003, The EMBO journal.

[53]  Martin Egli,et al.  Visualizing a circadian clock protein: crystal structure of KaiC and functional insights. , 2004, Molecular cell.

[54]  Martin Egli,et al.  Identification of key phosphorylation sites in the circadian clock protein KaiC by crystallographic and mutagenetic analyses. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[55]  Cheng Chi Lee,et al.  Reciprocal regulation of haem biosynthesis and the circadian clock in mammals , 2004, Nature.

[56]  Felix Naef,et al.  Circadian Gene Expression in Individual Fibroblasts Cell-Autonomous and Self-Sustained Oscillators Pass Time to Daughter Cells , 2004, Cell.