Molecular mechanism of the Neurospora circadian oscillator

Abstract

Circadian clocks are the internal time-keeping mechanisms for organisms to synchronize their cellular and physiological processes to the daily light/dark cycles. The molecular mechanisms underlying circadian clocks are remarkably similar in eukaryotes. Neurospora crassa, a filamentous fungus, is one of the best understood model organisms for circadian research. In recent years, accumulating data have revealed complex regulation in the Neurospora circadian clock at transcriptional, post-transcriptional, post-translational and epigenetic levels. Here we review the recent progress towards our understanding of the molecular mechanism of the Neurospora circadian oscillator. These advances have provided novel insights and furthered our understanding of the mechanism of eukaryotic circadian clocks.

Keywords

circadian clock / circadian oscillator / Neurospora crassa / eukaryotes

References

[1] Allada, R., and Meissner, R.A. (2005). Casein kinase 2, circadian clocks, and the flight from mutagenic light. Mol Cell Biochem 274, 141–149 .10.1007/s11010-005-2943-1
[2] Aronson, B.D., Johnson, K.A., and Dunlap, J.C. (1994a). Circadian clock locus frequency: protein encoded by a single open reading frame defines period length and temperature compensation. Proc Natl Acad Sci U S A 91, 7683–7687 .10.1073/pnas.91.16.7683
[3] Aronson, B.D., Johnson, K.A., Loros, J.J., and Dunlap, J.C. (1994b). Negative feedback defining a circadian clock: autoregulation of the clock gene frequency. Science 263, 1578–1584 .10.1126/science.8128244
[4] Baker, C.L., Kettenbach, A.N., Loros, J.J., Gerber, S.A., and Dunlap, J.C. (2009). Quantitative proteomics reveals a dynamic interactome and phase-specific phosphorylation in the Neurospora circadian clock. Mol Cell 34, 354–363 .10.1016/j.molcel.2009.04.023
[5] Ballario, P., Vittorioso, P., Magrelli, A., Talora, C., Cabibbo, A., and Macino, G. (1996). White collar-1, a central regulator of blue light responses in Neurospora, is a zinc finger protein. EMBO J 15, 1650–1657 .
[6] Belden, W.J., Larrondo, L.F., Froehlich, A.C., Shi, M., Chen, C.H., Loros, J.J., and Dunlap, J.C. (2007a). The band mutation in Neurospora crassa is a dominant allele of ras-1 implicating RAS signaling in circadian output. Genes Dev 21, 1494–1505 .10.1101/gad.1551707
[7] Belden, W.J., Loros, J.J., and Dunlap, J.C. (2007b). Execution of the circadian negative feedback loop in Neurospora requires the ATP-dependent chromatin-remodeling enzyme CLOCKSWITCH. Mol Cell 25, 587–600 .10.1016/j.molcel.2007.01.010
[8] Bell-Pedersen, D., Dunlap, J.C., and Loros, J.J. (1996). Distinct cis-acting elements mediate clock, light, and developmental regulation of the Neurospora crassa eas (ccg-2) gene. Mol Cell Biol 16, 513–521 .
[9] Bell-Pedersen, D., Cassone, V.M., Earnest, D.J., Golden, S.S., Hardin, P.E., Thomas, T.L., and Zoran, M.J. (2005). Circadian rhythms from multiple oscillators: lessons from diverse organisms. Nat Rev Genet 6, 544–556 .10.1038/nrg1633
[10] Brown, S.A., Ripperger, J., Kadener, S., Fleury-Olela, F., Vilbois, F., Rosbash, M., and Schibler, U. (2005). PERIOD1-associated proteins modulate the negative limb of the mammalian circadian oscillator. Science 308, 693–696 .10.1126/science.1107373
[11] Brunner, M., and Schafmeier, T. (2006). Transcriptional and post-transcriptional regulation of the circadian clock of cyanobacteria and Neurospora. Genes Dev 20, 1061–1074 .10.1101/gad.1410406
[12] Cha, J., Huang, G., Guo, J., and Liu, Y. (2007). Posttranslational control of the Neurospora circadian clock. Cold Spring Harb Symp Quant Biol 72, 185–191 .10.1101/sqb.2007.72.010
[13] Cha, J., Chang, S.S., Huang, G., Cheng, P., and Liu, Y. (2008). Control of WHITE COLLAR localization by phosphorylation is a critical step in the circadian negative feedback process. EMBO J 27, 3246–3255 .10.1038/emboj.2008.245
[14] Cheng, P., Yang, Y., Heintzen, C., and Liu, Y. (2001a). Coiled-coil domain-mediated FRQ-FRQ interaction is essential for its circadian clock function in Neurospora. EMBO J 20, 101–108 .10.1093/emboj/20.1.101
[15] Cheng, P., Yang, Y., and Liu, Y. (2001b). Interlocked feedback loops contribute to the robustness of the Neurospora circadian clock. Proc Natl Acad Sci U S A 98, 7408–7413 .10.1073/pnas.121170298
[16] Cheng, P., Yang,Y., Gardner, K.H., and Liu, Y. (2002). PAS domain-mediated WC-1/WC-2 interaction is essential for maintaining the steady-state level of WC-1 and the function of both proteins in circadian clock and light responses of Neurospora. Mol Cell Biol 22, 517–524 .10.1128/MCB.22.2.517-524.2002
[17] Cheng, P., He, Q., Yang, Y., Wang, L., and Liu, Y. (2003a). Functional conservation of light, oxygen, or voltage domains in light sensing. Proc Natl Acad Sci U S A 100, 5938–5943 .10.1073/pnas.1031791100
[18] Cheng, P., Yang, Y., Wang, L., He, Q., and Liu, Y. (2003b). WHITE COLLAR-1, a multifunctional Neurospora protein involved in the circadian feedback loops, light sensing, and transcription repression of wc-2. J Biol Chem 278, 3801–3808 .10.1074/jbc.M209592200
[19] Cheng, P., He, Q., He, Q., Wang, L., and Liu, Y. (2005). Regulation of the Neurospora circadian clock by an RNA helicase. Genes Dev 19, 234–241 .10.1101/gad.1266805
[20] Cohen, P.T. (2002). Protein phosphatase 1—targeted in many directions. J Cell Sci 115, 241–256 .
[21] Colot, H.V., Loros, J.J., and Dunlap, J.C. (2005). Temperature-modulated alternative splicing and promoter use in the Circadian clock gene frequency. Mol Biol Cell 16, 5563–5571 .10.1091/mbc.E05-08-0756
[22] Cope, G.A., and Deshaies, R.J. (2003). COP9 signalosome: a multifunctional regulator of SCF and other cullin-based ubiquitin ligases. Cell 114, 663–671 .10.1016/S0092-8674(03)00722-0
[23] Crosthwaite, S.K., Dunlap, J.C., and Loros, J.J. (1997). Neurospora wc-1 and wc-2: transcription, photoresponses, and the origins of circadian rhythmicity. Science 276, 763–769 .10.1126/science.276.5313.763
[24] de Paula, R.M., Lamb, T.M., Bennett, L., and Bell-Pedersen, D. (2008). A connection between MAPK pathways and circadian clocks. Cell Cycle 7, 2630–2634 .
[25] Diernfellner, A., Colot, H.V., Dintsis, O., Loros, J.J., Dunlap, J.C., and Brunner, M. (2007). Long and short isoforms of Neurospora clock protein FRQ support temperature-compensated circadian rhythms. FEBS Lett 581, 5759–5764 .10.1016/j.febslet.2007.11.043
[26] Diernfellner, A.C., Querfurth, C., Salazar, C., H?fer, T., and Brunner, M. (2009). Phosphorylation modulates rapid nucleocytoplasmic shuttling and cytoplasmic accumulation of Neurospora clock protein FRQ on a circadian time scale. Genes Dev 23, 2192–2200 .10.1101/gad.538209
[27] Dunlap, J.C., and Loros, J.J. (2004). The neurospora circadian system. J Biol Rhythms 19, 414–424 .10.1177/0748730404269116
[28] Dunlap, J.C., Loros, J.J., Colot, H.V., Mehra, A., Belden, W.J., Shi, M., Hong, C.I., Larrondo, L.F., Baker, C.L., Chen, C.H., . (2007). A circadian clock in Neurospora: how genes and proteins cooperate to produce a sustained, entrainable, and compensated biological oscillator with a period of about a day. Cold Spring Harb Symp Quant Biol 72, 57–68 .10.1101/sqb.2007.72.072
[29] Eide, E.J., Woolf, M.F., Kang, H., Woolf, P., Hurst, W., Camacho, F., Vielhaber, E.L., Giovanni, A., and Virshup, D.M. (2005). Control of mammalian circadian rhythm by CKIepsilon-regulated proteasome-mediated PER2 degradation. Mol Cell Biol 25, 2795–2807 .10.1128/MCB.25.7.2795-2807.2005
[30] Etchegaray, J.P., Lee, C., Wade, P.A., and Reppert, S.M. (2003). Rhythmic histone acetylation underlies transcription in the mammalian circadian clock. Nature 421, 177–182 .10.1038/nature01314
[31] Fang, Y., Sathyanarayanan, S., and Sehgal, A. (2007). Post-translational regulation of the Drosophila circadian clock requires protein phosphatase 1 (PP1). Genes Dev 21, 1506–1518 .10.1101/gad.1541607
[32] Foster, R.G. (2004). Seeing the light...in a new way. J Neuroendocrinol 16, 179–180 .10.1111/j.0953-8194.2004.01141.x
[33] Franchi, L., Fulci, V., and Macino, G. (2005). Protein kinase C modulates light responses in Neurospora by regulating the blue light photoreceptor WC-1. Mol Microbiol 56, 334–345 .10.1111/j.1365-2958.2005.04545.x
[34] Froehlich, A.C., Liu, Y., Loros, J.J., and Dunlap, J.C. (2002). White Collar-1, a circadian blue light photoreceptor, binding to the frequency promoter. Science 297, 815–819 .10.1126/science.1073681
[35] Froehlich, A.C., Loros, J.J., and Dunlap, J.C. (2003). Rhythmic binding of a WHITE COLLAR-containing complex to the frequency promoter is inhibited by FREQUENCY. Proc Natl Acad Sci U S A 100, 5914–5919 .10.1073/pnas.1030057100
[36] Garceau, N.Y., Liu, Y., Loros, J.J., and Dunlap, J.C. (1997). Alternative initiation of translation and time-specific phosphorylation yield multiple forms of the essential clock protein FREQUENCY. Cell 89, 469–476 .10.1016/S0092-8674(00)80227-5
[37] Glossop, N.R., Lyons, L.C., and Hardin, P.E. (1999). Interlocked feedback loops within the Drosophila circadian oscillator. Science 286, 766–768 .10.1126/science.286.5440.766
[38] Gooch, V.D., Wehseler, R.A., and Gross, C.G. (1994). Temperature effects on the resetting of the phase of the Neurospora circadian rhythm. J Biol Rhythms 9, 83–94 .10.1177/074873049400900108
[39] G?rl, M., Merrow, M., Huttner, B., Johnson, J., Roenneberg, T., and Brunner, M. (2001). A PEST-like element in FREQUENCY determines the length of the circadian period in Neurospora crassa. EMBO J 20, 7074–7084 .10.1093/emboj/20.24.7074
[40] Grima, B., Lamouroux, A., Chélot, E., Papin, C., Limbourg-Bouchon, B., and Rouyer, F. (2002). The F-box protein slimb controls the levels of clock proteins period and timeless. Nature 420, 178–182 .10.1038/nature01122
[41] Guo, J., Cheng, P., Yuan, H., and Liu, Y. (2009). The exosome regulates circadian gene expression in a posttranscriptional negative feedback loop. Cell 138, 1236–1246 .10.1016/j.cell.2009.06.043
[42] Guo, J., Cheng, P., and Liu, Y. (2010). Functional significance of FRH in regulating the phosphorylation and stability of the neurospora circadian clock protein FRQ. J Biol Chem. 285, 11508–11515. .10.1074/jbc.M109.071688
[43] Harmer, S.L. (2009). The circadian system in higher plants. Annu Rev Plant Biol 60, 357–377 .10.1146/annurev.arplant.043008.092054
[44] He, Q., and Liu, Y. (2005a). Degradation of the Neurospora circadian clock protein FREQUENCY through the ubiquitin-proteasome pathway. Biochem Soc Trans 33, 953–956 .10.1042/BST20050953
[45] He, Q., and Liu, Y. (2005b). Molecular mechanism of light responses in Neurospora: from light-induced transcription to photoadaptation. Genes Dev 19, 2888–2899 .10.1101/gad.1369605
[46] He, Q., Cheng, P., Yang, Y., Wang, L., Gardner, K.H., and Liu, Y. (2002). White collar-1, a DNA binding transcription factor and a light sensor. Science 297, 840–843 .10.1126/science.1072795
[47] He, Q., Cheng, P., Yang, Y., He, Q., Yu, H., and Liu, Y. (2003). FWD1-mediated degradation of FREQUENCY in Neurospora establishes a conserved mechanism for circadian clock regulation. EMBO J 22, 4421–4430 .10.1093/emboj/cdg425
[48] He, Q., Cheng, P., He, Q., and Liu, Y. (2005a). The COP9 signalosome regulates the Neurospora circadian clock by controlling the stability of the SCFFWD-1 complex. Genes Dev 19, 1518–1531 .10.1101/gad.1322205
[49] He, Q., Shu, H., Cheng, P., Chen, S., Wang, L., and Liu, Y. (2005b). Light-independent phosphorylation of WHITE COLLAR-1 regulates its function in the Neurospora circadian negative feedback loop. J Biol Chem 280, 17526–17532 .10.1074/jbc.M414010200
[50] He, Q., Cha, J., He, Q., Lee, H.C., Yang, Y., and Liu, Y. (2006). CKI and CKII mediate the FREQUENCY-dependent phosphorylation of the WHITE COLLAR complex to close the Neurospora circadian negative feedback loop. Genes Dev 20, 2552–2565 .10.1101/gad.1463506
[51] Heintzen, C., and Liu, Y. (2007). The Neurospora crassa circadian clock. Adv Genet 58, 25–66 .10.1016/S0065-2660(06)58002-2
[52] Hong, C.I., Ruoff, P., Loros, J.J., and Dunlap, J.C. (2008). Closing the circadian negative feedback loop: FRQ-dependent clearance of WC-1 from the nucleus. Genes Dev 22, 3196–3204 .10.1101/gad.1706908
[53] Houseley, J., LaCava, J., and Tollervey, D. (2006). RNA-quality control by the exosome. Nat Rev Mol Cell Biol 7, 529–539 .10.1038/nrm1964
[54] Huang, G., Wang, L., and Liu, Y. (2006). Molecular mechanism of suppression of circadian rhythms by a critical stimulus. EMBO J 25, 5349–5357 .10.1038/sj.emboj.7601397
[55] Huang, G., Chen, S., Li, S., Cha, J., Long, C., Li, L., He, Q., and Liu, Y. (2007). Protein kinase A and casein kinases mediate sequential phosphorylation events in the circadian negative feedback loop. Genes Dev 21, 3283–3295 .10.1101/gad.1610207
[56] Káldi, K., González, B.H., and Brunner, M. (2006). Transcriptional regulation of the Neurospora circadian clock gene wc-1 affects the phase of circadian output. EMBO Rep 7, 199–204 .10.1038/sj.embor.7400595
[57] Kloss, B., Price, J.L., Saez, L., Blau, J., Rothenfluh, A., Wesley, C.S., and Young, M.W. (1998). The Drosophila clock gene double-time encodes a protein closely related to human casein kinase Iepsilon. Cell 94, 97–107 .10.1016/S0092-8674(00)81225-8
[58] Ko, H.W., Jiang, J., and Edery, I. (2002). Role for Slimb in the degradation of Drosophila Period protein phosphorylated by Doubletime. Nature 420, 673–678 .10.1038/nature01272
[59] Kramer, C., Loros, J.J., Dunlap, J.C., and Crosthwaite, S.K. (2003). Role for antisense RNA in regulating circadian clock function in Neurospora crassa. Nature 421, 948–952 .10.1038/nature01427
[60] LaCava, J., Houseley, J., Saveanu, C., Petfalski, E., Thompson, E., Jacquier, A., and Tollervey, D. (2005). RNA degradation by the exosome is promoted by a nuclear polyadenylation complex. Cell 121, 713–724 .10.1016/j.cell.2005.04.029
[61] Lauter, F.R., and Russo, V.E. (1990). Light-induced dephosphorylation of a 33 kDa protein in the wild-type strain of Neurospora crassa: the regulatory mutants wc-1 and wc-2 are abnormal. J Photochem Photobiol B 5, 95–103 .10.1016/1011-1344(90)85008-K
[62] Lee, K., Loros, J.J., and Dunlap, J.C. (2000). Interconnected feedback loops in the Neurospora circadian system. Science 289, 107–110 .10.1126/science.289.5476.107
[63] Levine, J.D. (2004). Sharing time on the fly. Curr Opin Cell Biol 16, 210–216 .10.1016/j.ceb.2004.02.009
[64] Linden, H., and Macino, G. (1997). White collar 2, a partner in blue-light signal transduction, controlling expression of light-regulated genes in Neurospora crassa. EMBO J 16, 98–109 .10.1093/emboj/16.1.98
[65] Liu, Y. (2003). Molecular mechanisms of entrainment in the Neurospora circadian clock. J Biol Rhythms 18, 195–205 .10.1177/0748730403018003002
[66] Liu, Y., and Bell-Pedersen, D. (2006). Circadian rhythms in Neurospora crassa and other filamentous fungi. Eukaryot Cell 5, 1184–1193 .10.1128/EC.00133-06
[67] Liu, Y., Garceau, N.Y., Loros, J.J., and Dunlap, J.C. (1997). Thermally regulated translational control of FRQ mediates aspects of temperature responses in the neurospora circadian clock. Cell 89, 477–486 .10.1016/S0092-8674(00)80228-7
[68] Liu, Y., Loros, J., and Dunlap, J.C. (2000). Phosphorylation of the Neurospora clock protein FREQUENCY determines its degradation rate and strongly influences the period length of the circadian clock. Proc Natl Acad Sci U S A 97, 234–239 .10.1073/pnas.97.1.234
[69] Loros, J.J., and Dunlap, J.C. (2001). Genetic and molecular analysis of circadian rhythms in Neurospora. Annu Rev Physiol 63, 757–794 .10.1146/annurev.physiol.63.1.757
[70] Lowrey, P.L., and Takahashi, J.S. (2000). Genetics of the mammalian circadian system: Photic entrainment, circadian pacemaker mechanisms, and posttranslational regulation. Annu Rev Genet 34, 533–562 .10.1146/annurev.genet.34.1.533
[71] Luo, C., Loros, J.J., and Dunlap, J.C. (1998). Nuclear localization is required for function of the essential clock protein FRQ. EMBO J 17, 1228–1235 .10.1093/emboj/17.5.1228
[72] Mehra, A., Baker, C.L., Loros, J.J., and Dunlap, J.C. (2009a). Post-translational modifications in circadian rhythms. Trends Biochem Sci 34, 483–490 .10.1016/j.tibs.2009.06.006
[73] Mehra, A., Shi, M., Baker, C.L., Colot, H.V., Loros, J.J., and Dunlap, J.C. (2009b). A role for casein kinase 2 in the mechanism underlying circadian temperature compensation. Cell 137, 749–760 .10.1016/j.cell.2009.03.019
[74] Neiss, A., Schafmeier, T., and Brunner, M. (2008). Transcriptional regulation and function of the Neurospora clock gene white collar 2 and its isoforms. EMBO Rep 9, 788–794 .10.1038/embor.2008.113
[75] Pregueiro, A.M., Liu, Q., Baker, C.L., Dunlap, J.C., and Loros, J.J. (2006). The Neurospora checkpoint kinase 2: a regulatory link between the circadian and cell cycles. Science 313, 644–649 .10.1126/science.1121716
[76] Price, J.L., Blau, J., Rothenfluh, A., Abodeely, M., Kloss, B., and Young, M.W. (1998). Double-time is a novel Drosophila clock gene that regulates PERIOD protein accumulation. Cell 94, 83–95 .10.1016/S0092-8674(00)81224-6
[77] Querfurth, C., Diernfellner, A., Heise, F., Lauinger, L., Neiss, A., Tataroglu, O., Brunner, M., and Schafmeier, T. (2007). Posttranslational regulation of Neurospora circadian clock by CK1a-dependent phosphorylation. Cold Spring Harb Symp Quant Biol 72, 177–183 .10.1101/sqb.2007.72.025
[78] Reppert, S.M. (2006). A colorful model of the circadian clock. Cell 124, 233–236 .10.1016/j.cell.2006.01.009
[79] Sargent, M.L., and Woodward, D.O. (1969). Genetic determinants of circadian rhythmicity in Neurospora. J Bacteriol 97, 861–866 .
[80] Sargent, M.L., Briggs, W.R., and Woodward, D.O. (1966). Circadian nature of a rhythm expressed by an invertaseless strain of Neurospora crassa. Plant Physiol 41, 1343–1349 .10.1104/pp.41.8.1343
[81] Sathyanarayanan, S., Zheng, X., Xiao, R., and Sehgal, A. (2004). Posttranslational regulation of Drosophila PERIOD protein by protein phosphatase 2A. Cell 116, 603–615 .10.1016/S0092-8674(04)00128-X
[82] Schafmeier, T., Haase, A., Káldi, K., Scholz, J., Fuchs, M., and Brunner, M. (2005). Transcriptional feedback of Neurospora circadian clock gene by phosphorylation-dependent inactivation of its transcription factor. Cell 122, 235–246 .10.1016/j.cell.2005.05.032
[83] Schafmeier, T., Diernfellner, A., Sch?fer, A., Dintsis, O., Neiss, A., and Brunner, M. (2008). Circadian activity and abundance rhythms of the Neurospora clock transcription factor WCC associated with rapid nucleo-cytoplasmic shuttling. Genes Dev 22, 3397–3402 .10.1101/gad.507408
[84] Shearman, L.P., Sriram, S., Weaver, D.R., Maywood, E.S., Chaves, I., Zheng, B., Kume, K., Lee, C.C., van der Horst, G.T., Hastings, M.H., . (2000). Interacting molecular loops in the mammalian circadian clock. Science 288, 1013–1019 .10.1126/science.288.5468.1013
[85] Shi, M., Collett, M., Loros, J.J., and Dunlap, J.C. (2009). FRQ-interacting RNA helicase (FRH) mediates negative and positive feedback in the neurospora circadian clock. Genetics 184, 351–36110.1534/genetics.109.111393
[86] Shirogane, T., Jin, J., Ang, X.L., and Harper, J.W. (2005). SCFbeta-TRCP controls clock-dependent transcription via casein kinase 1-dependent degradation of the mammalian period-1 (Per1) protein. J Biol Chem 280, 26863–26872 .10.1074/jbc.M502862200
[87] Talora, C., Franchi, L., Linden, H., Ballario, P., and Macino, G. (1999). Role of a white collar-1-white collar-2 complex in blue-light signal transduction. EMBO J 18, 4961–4968 .10.1093/emboj/18.18.4961
[88] Tang, C.T., Li, S., Long, C., Cha, J., Huang, G., Li, L., Chen, S., and Liu, Y. (2009). Setting the pace of the Neurospora circadian clock by multiple independent FRQ phosphorylation events. Proc Natl Acad Sci USA 106, 10722–10727 .10.1073/pnas.0904898106
[89] Taylor, S.S., Kim, C., Vigil, D., Haste, N.M., Yang, J., Wu, J., and Anand, G.S. (2005). Dynamics of signaling by PKA. Biochim Biophys Acta 1754, 25–37 .
[90] Tralau, T., Lanthaler, K., Robson, G.D., and Crosthwaite, S.K. (2007). Circadian rhythmicity during prolonged chemostat cultivation of neurospora crassa. Fungal Genet Biol 44, 754–763 .10.1016/j.fgb.2006.11.003
[91] Vanácová, S., Wolf, J., Martin, G., Blank, D., Dettwiler, S., Friedlein, A., Langen, H., Keith, G., and Keller, W. (2005). A new yeast poly(A) polymerase complex involved in RNA quality control. PLoS Biol 3, e189.10.1371/journal.pbio.0030189
[92] Vanselow, K., Vanselow, J.T., Westermark, P.O., Reischl, S., Maier, B., Korte, T., Herrmann, A., Herzel, H., Schlosser, A., and Kramer, A. (2006). Differential effects of PER2 phosphorylation: molecular basis for the human familial advanced sleep phase syndrome (FASPS). Genes Dev 20, 2660–2672 .10.1101/gad.397006
[93] Vitalini, M.W., Morgan, L.W., March, I.J., and Bell-Pedersen, D. (2004). A genetic selection for circadian output pathway mutations in Neurospora crassa. Genetics 167, 119–129 .10.1534/genetics.167.1.119
[94] Williams, S.B. (2007). A circadian timing mechanism in the cyanobacteria. Adv Microb Physiol 52, 229–296 .10.1016/S0065-2911(06)52004-1
[95] Wu, G., Xu, G., Schulman, B.A., Jeffrey, P.D., Harper, J.W., and Pavletich, N.P. (2003). Structure of a beta-TrCP1-Skp1-beta-catenin complex: destruction motif binding and lysine specificity of the SCF(beta-TrCP1) ubiquitin ligase. Mol Cell 11, 1445–1456 .10.1016/S1097-2765(03)00234-X
[96] Xu, Y., Padiath, Q.S., Shapiro, R.E., Jones, C.R., Wu, S.C., Saigoh, N., Saigoh, K., Ptácek, L.J., and Fu, Y.H. (2005). Functional consequences of a CKIdelta mutation causing familial advanced sleep phase syndrome. Nature 434, 640–644 .10.1038/nature03453
[97] Xu, Y., Toh, K.L., Jones, C.R., Shin, J.Y., Fu, Y.H., and Ptácek, L.J. (2007). Modeling of a human circadian mutation yields insights into clock regulation by PER2. Cell 128, 59–70 .10.1016/j.cell.2006.11.043
[98] Yang, Y., Cheng, P., Zhi, G., and Liu, Y. (2001). Identification of a calcium/calmodulin-dependent protein kinase that phosphorylates the Neurospora circadian clock protein FREQUENCY. J Biol Chem 276, 41064–41072 .10.1074/jbc.M106905200
[99] Yang, Y., Cheng, P., and Liu, Y. (2002). Regulation of the Neurospora circadian clock by casein kinase II. Genes Dev 16, 994–1006 .10.1101/gad.965102
[100] Yang, Y., Cheng, P., He, Q., Wang, L., and Liu, Y. (2003). Phosphorylation of FREQUENCY protein by casein kinase II is necessary for the function of the Neurospora circadian clock. Mol Cell Biol 23, 6221–6228 .10.1128/MCB.23.17.6221-6228.2003
[101] Yang, Y., He, Q., Cheng, P., Wrage, P., Yarden, O., and Liu, Y. (2004). Distinct roles for PP1 and PP2A in the Neurospora circadian clock. Genes Dev 18, 255–260 .10.1101/gad.1152604
[102] Young, M.W., and Kay, S.A. (2001). Time zones: a comparative genetics of circadian clocks. Nat Rev Genet 2, 702–715 .10.1038/35088576