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. 2010 Apr 1;1(4):331–341. doi: 10.1007/s13238-010-0053-7

Molecular mechanism of the Neurospora circadian oscillator

Jinhu Guo 1, Yi Liu 1,✉
PMCID: PMC4875101  PMID: 21203945

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, posttranscriptional, 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., Meissner R.A. Casein kinase 2, circadian clocks, and the flight from mutagenic light. Mol Cell Biochem. 2005;274:141–149. doi: 10.1007/s11010-005-2943-1. [DOI] [PubMed] [Google Scholar]
  2. Aronson B.D., Johnson K.A., Dunlap J.C. 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. 1994;91:7683–7687. doi: 10.1073/pnas.91.16.7683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Aronson B.D., Johnson K.A., Loros J.J., Dunlap J.C. Negative feedback defining a circadian clock: autoregulation of the clock gene frequency. Science. 1994;263:1578–1584. doi: 10.1126/science.8128244. [DOI] [PubMed] [Google Scholar]
  4. Baker C.L., Kettenbach A.N., Loros J.J., Gerber S.A., Dunlap J.C. Quantitative proteomics reveals a dynamic interactome and phase-specific phosphorylation in the Neurospora circadian clock. Mol Cell. 2009;34:354–363. doi: 10.1016/j.molcel.2009.04.023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ballario P., Vittorioso P., Magrelli A., Talora C., Cabibbo A., Macino G. White collar-1, a central regulator of blue light responses in Neurospora, is a zinc finger protein. EMBO J. 1996;15:1650–1657. [PMC free article] [PubMed] [Google Scholar]
  6. Belden W.J., Larrondo L.F., Froehlich A.C., Shi M., Chen C.H., Loros J.J., Dunlap J.C. The band mutation in Neurospora crassa is a dominant allele of ras-1 implicating RAS signaling in circadian output. Genes Dev. 2007;21:1494–1505. doi: 10.1101/gad.1551707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Belden W.J., Loros J.J., Dunlap J.C. Execution of the circadian negative feedback loop in Neurospora requires the ATP-dependent chromatin-remodeling enzyme CLOCKSWITCH. Mol Cell. 2007;25:587–600. doi: 10.1016/j.molcel.2007.01.010. [DOI] [PubMed] [Google Scholar]
  8. Bell-Pedersen D., Dunlap J.C., Loros J.J. Distinct cisacting elements mediate clock, light, and developmental regulation of the Neurospora crassa eas (ccg-2) gene. Mol Cell Biol. 1996;16:513–521. doi: 10.1128/MCB.16.2.513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bell-Pedersen D., Cassone V.M., Earnest D.J., Golden S.S., Hardin P.E., Thomas T.L., Zoran M.J. Circadian rhythms from multiple oscillators: lessons from diverse organisms. Nat Rev Genet. 2005;6:544–556. doi: 10.1038/nrg1633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Brown S.A., Ripperger J., Kadener S., Fleury-Olela F., Vilbois F., Rosbash M., Schibler U. PERIOD1-associated proteins modulate the negative limb of the mammalian circadian oscillator. Science. 2005;308:693–696. doi: 10.1126/science.1107373. [DOI] [PubMed] [Google Scholar]
  11. Brunner M., Schafmeier T. Transcriptional and posttranscriptional regulation of the circadian clock of cyanobacteria and Neurospora. Genes Dev. 2006;20:1061–1074. doi: 10.1101/gad.1410406. [DOI] [PubMed] [Google Scholar]
  12. Cha J., Huang G., Guo J., Liu Y. Posttranslational control of the Neurospora circadian clock. Cold Spring Harb Symp Quant Biol. 2007;72:185–191. doi: 10.1101/sqb.2007.72.010. [DOI] [PubMed] [Google Scholar]
  13. Cha J., Chang S.S., Huang G., Cheng P., Liu Y. Control of WHITE COLLAR localization by phosphorylation is a critical step in the circadian negative feedback process. EMBO J. 2008;27:3246–3255. doi: 10.1038/emboj.2008.245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Cheng P., Yang Y., Heintzen C., Liu Y. Coiled-coil domain-mediated FRQ-FRQ interaction is essential for its circadian clock function in Neurospora. EMBO J. 2001;20:101–108. doi: 10.1093/emboj/20.1.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Cheng P., Yang Y., Liu Y. Interlocked feedback loops contribute to the robustness of the Neurospora circadian clock. Proc Natl Acad Sci U S A. 2001;98:7408–7413. doi: 10.1073/pnas.121170298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Cheng P., Yang Y., Gardner K.H., Liu Y. PAS domainmediated 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. 2002;22:517–524. doi: 10.1128/MCB.22.2.517-524.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Cheng P., He Q., Yang Y., Wang L., Liu Y. Functional conservation of light, oxygen, or voltage domains in light sensing. Proc Natl Acad Sci U S A. 2003;100:5938–5943. doi: 10.1073/pnas.1031791100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Cheng P., Yang Y., Wang L., He Q., Liu Y. WHITE COLLAR-1, a multifunctional Neurospora protein involved in the circadian feedback loops, light sensing, and transcription repression of wc-2. J Biol Chem. 2003;278:3801–3808. doi: 10.1074/jbc.M209592200. [DOI] [PubMed] [Google Scholar]
  19. Cheng P., He Q., He Q., Wang L., Liu Y. Regulation of the Neurospora circadian clock by an RNA helicase. Genes Dev. 2005;19:234–241. doi: 10.1101/gad.1266805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Cohen P.T. Protein phosphatase 1—targeted in many directions. J Cell Sci. 2002;115:241–256. doi: 10.1242/jcs.115.2.241. [DOI] [PubMed] [Google Scholar]
  21. Colot H.V., Loros J.J., Dunlap J.C. Temperaturemodulated alternative splicing and promoter use in the Circadian clock gene frequency. Mol Biol Cell. 2005;16:5563–5571. doi: 10.1091/mbc.E05-08-0756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Cope G.A., Deshaies R.J. COP9 signalosome: a multifunctional regulator of SCF and other cullin-based ubiquitin ligases. Cell. 2003;114:663–671. doi: 10.1016/S0092-8674(03)00722-0. [DOI] [PubMed] [Google Scholar]
  23. Crosthwaite S.K., Dunlap J.C., Loros J.J. Neurospora wc-1 and wc-2: transcription, photoresponses, and the origins of circadian rhythmicity. Science. 1997;276:763–769. doi: 10.1126/science.276.5313.763. [DOI] [PubMed] [Google Scholar]
  24. de Paula R.M., Lamb T.M., Bennett L., Bell-Pedersen D. A connection between MAPK pathways and circadian clocks. Cell Cycle. 2008;7:2630–2634. doi: 10.4161/cc.7.17.6516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Diernfellner A., Colot H.V., Dintsis O., Loros J.J., Dunlap J.C., Brunner M. Long and short isoforms of Neurospora clock protein FRQ support temperature-compensated circadian rhythms. FEBS Lett. 2007;581:5759–5764. doi: 10.1016/j.febslet.2007.11.043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Diernfellner A.C., Querfurth C., Salazar C., Höfer T., Brunner M. Phosphorylation modulates rapid nucleocytoplasmic shuttling and cytoplasmic accumulation of Neurospora clock protein FRQ on a circadian time scale. Genes Dev. 2009;23:2192–2200. doi: 10.1101/gad.538209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Dunlap J.C., Loros J.J. The neurospora circadian system. J Biol Rhythms. 2004;19:414–424. doi: 10.1177/0748730404269116. [DOI] [PubMed] [Google Scholar]
  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., et al. 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. 2007;72:57–68. doi: 10.1101/sqb.2007.72.072. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Eide E.J., Woolf M.F., Kang H., Woolf P., Hurst W., Camacho F., Vielhaber E.L., Giovanni A., Virshup D.M. Control of mammalian circadian rhythm by CKIepsilon-regulated proteasome-mediated PER2 degradation. Mol Cell Biol. 2005;25:2795–2807. doi: 10.1128/MCB.25.7.2795-2807.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Etchegaray J.P., Lee C., Wade P.A., Reppert S.M. Rhythmic histone acetylation underlies transcription in the mammalian circadian clock. Nature. 2003;421:177–182. doi: 10.1038/nature01314. [DOI] [PubMed] [Google Scholar]
  31. Fang Y., Sathyanarayanan S., Sehgal A. Posttranslational regulation of the Drosophila circadian clock requires protein phosphatase 1 (PP1) Genes Dev. 2007;21:1506–1518. doi: 10.1101/gad.1541607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Foster R.G. Seeing the light…in a new way. J Neuroendocrinol. 2004;16:179–180. doi: 10.1111/j.0953-8194.2004.01141.x. [DOI] [PubMed] [Google Scholar]
  33. Franchi L., Fulci V., Macino G. Protein kinase C modulates light responses in Neurospora by regulating the blue light photoreceptor WC-1. Mol Microbiol. 2005;56:334–345. doi: 10.1111/j.1365-2958.2005.04545.x. [DOI] [PubMed] [Google Scholar]
  34. Froehlich A.C., Liu Y., Loros J.J., Dunlap J.C. White Collar-1, a circadian blue light photoreceptor, binding to the frequency promoter. Science. 2002;297:815–819. doi: 10.1126/science.1073681. [DOI] [PubMed] [Google Scholar]
  35. Froehlich A.C., Loros J.J., Dunlap J.C. Rhythmic binding of a WHITE COLLAR-containing complex to the frequency promoter is inhibited by FREQUENCY. Proc Natl Acad Sci U S A. 2003;100:5914–5919. doi: 10.1073/pnas.1030057100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Garceau N.Y., Liu Y., Loros J.J., Dunlap J.C. Alternative initiation of translation and time-specific phosphorylation yield multiple forms of the essential clock protein FREQUENCY. Cell. 1997;89:469–476. doi: 10.1016/S0092-8674(00)80227-5. [DOI] [PubMed] [Google Scholar]
  37. Glossop N.R., Lyons L.C., Hardin P.E. Interlocked feedback loops within the Drosophila circadian oscillator. Science. 1999;286:766–768. doi: 10.1126/science.286.5440.766. [DOI] [PubMed] [Google Scholar]
  38. Gooch V.D., Wehseler R.A., Gross C.G. Temperature effects on the resetting of the phase of the Neurospora circadian rhythm. J Biol Rhythms. 1994;9:83–94. doi: 10.1177/074873049400900108. [DOI] [PubMed] [Google Scholar]
  39. Görl M., Merrow M., Huttner B., Johnson J., Roenneberg T., Brunner M. A PEST-like element in FREQUENCY determines the length of the circadian period in Neurospora crassa. EMBO J. 2001;20:7074–7084. doi: 10.1093/emboj/20.24.7074. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Grima B., Lamouroux A., Chélot E., Papin C., Limbourg-Bouchon B., Rouyer F. The F-box protein slimb controls the levels of clock proteins period and timeless. Nature. 2002;420:178–182. doi: 10.1038/nature01122. [DOI] [PubMed] [Google Scholar]
  41. Guo J., Cheng P., Yuan H., Liu Y. The exosome regulates circadian gene expression in a posttranscriptional negative feedback loop. Cell. 2009;138:1236–1246. doi: 10.1016/j.cell.2009.06.043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Guo J., Cheng P., Liu Y. Functional significance of FRH in regulating the phosphorylation and stability of the neurospora circadian clock protein FRQ. J Biol Chem. 2010;285:11508–11515. doi: 10.1074/jbc.M109.071688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Harmer S.L. The circadian system in higher plants. Annu Rev Plant Biol. 2009;60:357–377. doi: 10.1146/annurev.arplant.043008.092054. [DOI] [PubMed] [Google Scholar]
  44. He Q., Liu Y. Degradation of the Neurospora circadian clock protein FREQUENCY through the ubiquitin-proteasome pathway. Biochem Soc Trans. 2005;33:953–956. doi: 10.1042/BST0330953. [DOI] [PubMed] [Google Scholar]
  45. He Q., Liu Y. Molecular mechanism of light responses in Neurospora: from light-induced transcription to photoadaptation. Genes Dev. 2005;19:2888–2899. doi: 10.1101/gad.1369605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. He Q., Cheng P., Yang Y., Wang L., Gardner K.H., Liu Y. White collar-1, a DNA binding transcription factor and a light sensor. Science. 2002;297:840–843. doi: 10.1126/science.1072795. [DOI] [PubMed] [Google Scholar]
  47. He Q., Cheng P., Yang Y., He Q., Yu H., Liu Y. FWD1-mediated degradation of FREQUENCY in Neurospora establishes a conserved mechanism for circadian clock regulation. EMBO J. 2003;22:4421–4430. doi: 10.1093/emboj/cdg425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. He Q., Cheng P., He Q., Liu Y. The COP9 signalosome regulates the Neurospora circadian clock by controlling the stability of the SCFFWD-1 complex. Genes Dev. 2005;19:1518–1531. doi: 10.1101/gad.1322205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. He Q., Shu H., Cheng P., Chen S., Wang L., Liu Y. Light-independent phosphorylation of WHITE COLLAR-1 regulates its function in the Neurospora circadian negative feedback loop. J Biol Chem. 2005;280:17526–17532. doi: 10.1074/jbc.M414010200. [DOI] [PubMed] [Google Scholar]
  50. He Q., Cha J., He Q., Lee H.C., Yang Y., Liu Y. CKI and CKII mediate the FREQUENCY-dependent phosphorylation of the WHITE COLLAR complex to close the Neurospora circadian negative feedback loop. Genes Dev. 2006;20:2552–2565. doi: 10.1101/gad.1463506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Heintzen C., Liu Y. The Neurospora crassa circadian clock. Adv Genet. 2007;58:25–66. doi: 10.1016/S0065-2660(06)58002-2. [DOI] [PubMed] [Google Scholar]
  52. Hong C.I., Ruoff P., Loros J.J., Dunlap J.C. Closing the circadian negative feedback loop: FRQ-dependent clearance of WC-1 from the nucleus. Genes Dev. 2008;22:3196–3204. doi: 10.1101/gad.1706908. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Houseley J., LaCava J., Tollervey D. RNA-quality control by the exosome. Nat Rev Mol Cell Biol. 2006;7:529–539. doi: 10.1038/nrm1964. [DOI] [PubMed] [Google Scholar]
  54. Huang G., Wang L., Liu Y. Molecular mechanism of suppression of circadian rhythms by a critical stimulus. EMBO J. 2006;25:5349–5357. doi: 10.1038/sj.emboj.7601397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Huang G., Chen S., Li S., Cha J., Long C., Li L., He Q., Liu Y. Protein kinase A and casein kinases mediate sequential phosphorylation events in the circadian negative feedback loop. Genes Dev. 2007;21:3283–3295. doi: 10.1101/gad.1610207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Káldi K., González B.H., Brunner M. Transcriptional regulation of the Neurospora circadian clock gene wc-1 affects the phase of circadian output. EMBO Rep. 2006;7:199–204. doi: 10.1038/sj.embor.7400595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Kloss B., Price J.L., Saez L., Blau J., Rothenfluh A., Wesley C.S., Young M.W. The Drosophila clock gene double-time encodes a protein closely related to human casein kinase Iepsilon. Cell. 1998;94:97–107. doi: 10.1016/S0092-8674(00)81225-8. [DOI] [PubMed] [Google Scholar]
  58. Ko H.W., Jiang J., Edery I. Role for Slimb in the degradation of Drosophila Period protein phosphorylated by Doubletime. Nature. 2002;420:673–678. doi: 10.1038/nature01272. [DOI] [PubMed] [Google Scholar]
  59. Kramer C., Loros J.J., Dunlap J.C., Crosthwaite S.K. Role for antisense RNA in regulating circadian clock function in Neurospora crassa. Nature. 2003;421:948–952. doi: 10.1038/nature01427. [DOI] [PubMed] [Google Scholar]
  60. LaCava J., Houseley J., Saveanu C., Petfalski E., Thompson E., Jacquier A., Tollervey D. RNA degradation by the exosome is promoted by a nuclear polyadenylation complex. Cell. 2005;121:713–724. doi: 10.1016/j.cell.2005.04.029. [DOI] [PubMed] [Google Scholar]
  61. Lauter F.R., Russo V.E. 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. 1990;5:95–103. doi: 10.1016/1011-1344(90)85008-K. [DOI] [PubMed] [Google Scholar]
  62. Lee K., Loros J.J., Dunlap J.C. Interconnected feedback loops in the Neurospora circadian system. Science. 2000;289:107–110. doi: 10.1126/science.289.5476.107. [DOI] [PubMed] [Google Scholar]
  63. Levine J.D. Sharing time on the fly. Curr Opin Cell Biol. 2004;16:210–216. doi: 10.1016/j.ceb.2004.02.009. [DOI] [PubMed] [Google Scholar]
  64. Linden H., Macino G. White collar 2, a partner in bluelight signal transduction, controlling expression of light-regulated genes in Neurospora crassa. EMBO J. 1997;16:98–109. doi: 10.1093/emboj/16.1.98. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Liu Y. Molecular mechanisms of entrainment in the Neurospora circadian clock. J Biol Rhythms. 2003;18:195–205. doi: 10.1177/0748730403018003002. [DOI] [PubMed] [Google Scholar]
  66. Liu Y., Bell-Pedersen D. Circadian rhythms in Neurospora crassa and other filamentous fungi. Eukaryot Cell. 2006;5:1184–1193. doi: 10.1128/EC.00133-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Liu Y., Garceau N.Y., Loros J.J., Dunlap J.C. Thermally regulated translational control of FRQ mediates aspects of temperature responses in the neurospora circadian clock. Cell. 1997;89:477–486. doi: 10.1016/S0092-8674(00)80228-7. [DOI] [PubMed] [Google Scholar]
  68. Liu Y., Loros J., Dunlap J.C. 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. 2000;97:234–239. doi: 10.1073/pnas.97.1.234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Loros J.J., Dunlap J.C. Genetic and molecular analysis of circadian rhythms in Neurospora. Annu Rev Physiol. 2001;63:757–794. doi: 10.1146/annurev.physiol.63.1.757. [DOI] [PubMed] [Google Scholar]
  70. Lowrey P.L., Takahashi J.S. Genetics of the mammalian circadian system: Photic entrainment, circadian pacemaker mechanisms, and posttranslational regulation. Annu Rev Genet. 2000;34:533–562. doi: 10.1146/annurev.genet.34.1.533. [DOI] [PubMed] [Google Scholar]
  71. Luo C., Loros J.J., Dunlap J.C. Nuclear localization is required for function of the essential clock protein FRQ. EMBO J. 1998;17:1228–1235. doi: 10.1093/emboj/17.5.1228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Mehra A., Baker C.L., Loros J.J., Dunlap J.C. Posttranslational modifications in circadian rhythms. Trends Biochem Sci. 2009;34:483–490. doi: 10.1016/j.tibs.2009.06.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Mehra A., Shi M., Baker C.L., Colot H.V., Loros J.J., Dunlap J. C. A role for casein kinase 2 in the mechanism underlying circadian temperature compensation. Cell. 2009;137:749–760. doi: 10.1016/j.cell.2009.03.019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Neiss A., Schafmeier T., Brunner M. Transcriptional regulation and function of the Neurospora clock gene white collar 2 and its isoforms. EMBO Rep. 2008;9:788–794. doi: 10.1038/embor.2008.113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Pregueiro A.M., Liu Q., Baker C.L., Dunlap J.C., Loros J.J. The Neurospora checkpoint kinase 2: a regulatory link between the circadian and cell cycles. Science. 2006;313:644–649. doi: 10.1126/science.1121716. [DOI] [PubMed] [Google Scholar]
  76. Price J.L., Blau J., Rothenfluh A., Abodeely M., Kloss B., Young M.W. Double-time is a novel Drosophila clock gene that regulates PERIOD protein accumulation. Cell. 1998;94:83–95. doi: 10.1016/S0092-8674(00)81224-6. [DOI] [PubMed] [Google Scholar]
  77. Querfurth C., Diernfellner A., Heise F., Lauinger L., Neiss A., Tataroglu O., Brunner M., Schafmeier T. Posttranslational regulation of Neurospora circadian clock by CK1a-dependent phosphorylation. Cold Spring Harb Symp Quant Biol. 2007;72:177–183. doi: 10.1101/sqb.2007.72.025. [DOI] [PubMed] [Google Scholar]
  78. Reppert S.M. A colorful model of the circadian clock. Cell. 2006;124:233–236. doi: 10.1016/j.cell.2006.01.009. [DOI] [PubMed] [Google Scholar]
  79. Sargent M.L., Woodward D.O. Genetic determinants of circadian rhythmicity in Neurospora. J Bacteriol. 1969;97:861–866. doi: 10.1128/jb.97.2.861-866.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Sargent M.L., Briggs W.R., Woodward D.O. Circadian nature of a rhythm expressed by an invertaseless strain of Neurospora crassa. Plant Physiol. 1966;41:1343–1349. doi: 10.1104/pp.41.8.1343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Sathyanarayanan S., Zheng X., Xiao R., Sehgal A. Posttranslational regulation of Drosophila PERIOD protein by protein phosphatase 2A. Cell. 2004;116:603–615. doi: 10.1016/S0092-8674(04)00128-X. [DOI] [PubMed] [Google Scholar]
  82. Schafmeier T., Haase A., Káldi K., Scholz J., Fuchs M., Brunner M. Transcriptional feedback of Neurospora circadian clock gene by phosphorylation-dependent inactivation of its transcription factor. Cell. 2005;122:235–246. doi: 10.1016/j.cell.2005.05.032. [DOI] [PubMed] [Google Scholar]
  83. Schafmeier T., Diernfellner A., Schäfer A., Dintsis O., Neiss A., Brunner M. Circadian activity and abundance rhythms of the Neurospora clock transcription factor WCC associated with rapid nucleo-cytoplasmic shuttling. Genes Dev. 2008;22:3397–3402. doi: 10.1101/gad.507408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  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., et al. Interacting molecular loops in the mammalian circadian clock. Science. 2000;288:1013–1019. doi: 10.1126/science.288.5468.1013. [DOI] [PubMed] [Google Scholar]
  85. Shi M., Collett M., Loros J.J., Dunlap J.C. FRQ-interacting RNA helicase (FRH) mediates negative and positive feedback in the neurospora circadian clock. Genetics. 2009;184:351–361. doi: 10.1534/genetics.109.111393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  86. Shirogane T., Jin J., Ang X.L., Harper J.W. SCFbeta-TRCP controls clock-dependent transcription via casein kinase 1-dependent degradation of the mammalian period-1 (Per1) protein. J Biol Chem. 2005;280:26863–26872. doi: 10.1074/jbc.M502862200. [DOI] [PubMed] [Google Scholar]
  87. Talora C., Franchi L., Linden H., Ballario P., Macino G. Role of a white collar-1-white collar-2 complex in blue-light signal transduction. EMBO J. 1999;18:4961–4968. doi: 10.1093/emboj/18.18.4961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  88. Tang C.T., Li S., Long C., Cha J., Huang G., Li L., Chen S., Liu Y. Setting the pace of the Neurospora circadian clock by multiple independent FRQ phosphorylation events. Proc Natl Acad Sci USA. 2009;106:10722–10727. doi: 10.1073/pnas.0904898106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Taylor S.S., Kim C., Vigil D., Haste N.M., Yang J., Wu J., Anand G.S. Dynamics of signaling by PKA. Biochim Biophys Acta. 2005;1754:25–37. doi: 10.1016/j.bbapap.2005.08.024. [DOI] [PubMed] [Google Scholar]
  90. Tralau T., Lanthaler K., Robson G.D., Crosthwaite S.K. Circadian rhythmicity during prolonged chemostat cultivation of neurospora crassa. Fungal Genet Biol. 2007;44:754–763. doi: 10.1016/j.fgb.2006.11.003. [DOI] [PubMed] [Google Scholar]
  91. Vanácová S., Wolf J., Martin G., Blank D., Dettwiler S., Friedlein A., Langen H., Keith G., Keller W. A new yeast poly (A) polymerase complex involved in RNA quality control. PLoS Biol. 2005;3:e189. doi: 10.1371/journal.pbio.0030189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  92. Vanselow K., Vanselow J.T., Westermark P.O., Reischl S., Maier B., Korte T., Herrmann A., Herzel H., Schlosser A., Kramer A. Differential effects of PER2 phosphorylation: molecular basis for the human familial advanced sleep phase syndrome (FASPS) Genes Dev. 2006;20:2660–2672. doi: 10.1101/gad.397006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  93. Vitalini M.W., Morgan L.W., March I.J., Bell-Pedersen D. A genetic selection for circadian output pathway mutations in Neurospora crassa. Genetics. 2004;167:119–129. doi: 10.1534/genetics.167.1.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  94. Williams S.B. A circadian timing mechanism in the cyanobacteria. Adv Microb Physiol. 2007;52:229–296. doi: 10.1016/S0065-2911(06)52004-1. [DOI] [PubMed] [Google Scholar]
  95. Wu G., Xu G., Schulman B.A., Jeffrey P.D., Harper J.W., Pavletich N.P. Structure of a beta-TrCP1-Skp1-betacatenin complex: destruction motif binding and lysine specificity of the SCF(beta-TrCP1) ubiquitin ligase. Mol Cell. 2003;11:1445–1456. doi: 10.1016/S1097-2765(03)00234-X. [DOI] [PubMed] [Google Scholar]
  96. Xu Y., Padiath Q.S., Shapiro R.E., Jones C.R., Wu S.C., Saigoh N., Saigoh K., Ptácek L.J., Fu Y.H. Functional consequences of a CKIdelta mutation causing familial advanced sleep phase syndrome. Nature. 2005;434:640–644. doi: 10.1038/nature03453. [DOI] [PubMed] [Google Scholar]
  97. Xu Y., Toh K.L., Jones C.R., Shin J.Y., Fu Y.H., Ptácek L.J. Modeling of a human circadian mutation yields insights into clock regulation by PER2. Cell. 2007;128:59–70. doi: 10.1016/j.cell.2006.11.043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  98. Yang Y., Cheng P., Zhi G., Liu Y. Identification of a calcium/calmodulin-dependent protein kinase that phosphorylates the Neurospora circadian clock protein FREQUENCY. J Biol Chem. 2001;276:41064–41072. doi: 10.1074/jbc.M106905200. [DOI] [PubMed] [Google Scholar]
  99. Yang Y., Cheng P., Liu Y. Regulation of the Neurospora circadian clock by casein kinase II. Genes Dev. 2002;16:994–1006. doi: 10.1101/gad.965102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  100. Yang Y., Cheng P., He Q., Wang L., Liu Y. Phosphorylation of FREQUENCY protein by casein kinase II is necessary for the function of the Neurospora circadian clock. Mol Cell Biol. 2003;23:6221–6228. doi: 10.1128/MCB.23.17.6221-6228.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  101. Yang Y., He Q., Cheng P., Wrage P., Yarden O., Liu Y. Distinct roles for PP1 and PP2A in the Neurospora circadian clock. Genes Dev. 2004;18:255–260. doi: 10.1101/gad.1152604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  102. Young M.W., Kay S.A. Time zones: a comparative genetics of circadian clocks. Nat Rev Genet. 2001;2:702–715. doi: 10.1038/35088576. [DOI] [PubMed] [Google Scholar]

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