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Gene Review

per  -  period

Drosophila melanogaster

Synonyms: CG2647, CLK-6, Clk, Dmel\CG2647, EG:155E2.4, ...
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High impact information on per

  • We propose that Clock is uniquely able to induce and organize the core elements of interdependent feedback loops necessary for circadian rhythms [1].
  • We demonstrate in Drosophila that Clock misexpression in nai;ve brain regions induces circadian gene expression [1].
  • Role for Slimb in the degradation of Drosophila Period protein phosphorylated by Doubletime [2].
  • A conserved feature of animal clocks is that Period (Per) proteins undergo daily rhythms in phosphorylation and levels, events that are crucial for normal clock progression [2].
  • Here we present the crystal structure of a Drosophila PERIOD (dPER) fragment comprising two tandemly organized PAS (PER-ARNT-SIM) domains (PAS-A and PAS-B) and two additional C-terminal alpha helices (alphaE and alphaF) [3].

Biological context of per

  • Circadian rhythms are controlled by the periodic accumulation of Period proteins, which act as transcriptional repressors of Clock-dependent genes [4].
  • Clk was previously mapped, by meiotic recombination, very close to the period(per) locus on the X chromosome [5].
  • The Clk(ar) phenotype is caused by a splice site mutation that severely disrupts splicing and reduces Clk activity [6].

Associations of per with chemical compounds


Other interactions of per

  • Consistent with a direct action on the clock mechanism, we show that CK2beta is localized within clock neurons and that the clock proteins Period (Per) and Timeless (Tim) accumulate to abnormally high levels in the Andante mutant [9].
  • We cloned Clock, Bmal, and Timeless homologs (apClock, apBmal, and apTimeless) from the silkmoth Antheraea pernyi, from which a Period homolog (apPeriod) has already been cloned [10].
  • The Drosophila PERIOD (dPER) protein is phosphorylated by the serine?threonine protein kinase, DOUBLETIME (DBT) [11].
  • Two basic helix-loop-helix (bHLH) PAS (PER-ARNT-SIM) transcription factors, CLOCK and BMAL1, form the positive elements of the system and drive transcription of three Period and two Cryptochrome genes [12].
  • We propose that dCREB2 supports cycling of the Period/Timeless oscillator [13].

Analytical, diagnostic and therapeutic context of per


  1. Drosophila clock can generate ectopic circadian clocks. Zhao, J., Kilman, V.L., Keegan, K.P., Peng, Y., Emery, P., Rosbash, M., Allada, R. Cell (2003) [Pubmed]
  2. Role for Slimb in the degradation of Drosophila Period protein phosphorylated by Doubletime. Ko, H.W., Jiang, J., Edery, I. Nature (2002) [Pubmed]
  3. Crystal structure and interactions of the PAS repeat region of the Drosophila clock protein PERIOD. Yildiz, O., Doi, M., Yujnovsky, I., Cardone, L., Berndt, A., Hennig, S., Schulze, S., Urbanke, C., Sassone-Corsi, P., Wolf, E. Mol. Cell (2005) [Pubmed]
  4. SCFbeta-TRCP controls clock-dependent transcription via casein kinase 1-dependent degradation of the mammalian period-1 (Per1) protein. Shirogane, T., Jin, J., Ang, X.L., Harper, J.W. J. Biol. Chem. (2005) [Pubmed]
  5. Mapping the clock rhythm mutation to the period locus of Drosophila melanogaster by germline transformation. Dushay, M.S., Rosbash, M., Hall, J.C. J. Neurogenet. (1992) [Pubmed]
  6. A recessive mutant of Drosophila Clock reveals a role in circadian rhythm amplitude. Allada, R., Kadener, S., Nandakumar, N., Rosbash, M. EMBO J. (2003) [Pubmed]
  7. Sensitized increase of period gene expression in the mouse caudate/putamen caused by repeated injection of methamphetamine. Nikaido, T., Akiyama, M., Moriya, T., Shibata, S. Mol. Pharmacol. (2001) [Pubmed]
  8. In search of clinal variation in the period and clock timing genes in Australian Drosophila melanogaster populations. Weeks, A.R., McKechnie, S.W., Hoffmann, A.A. J. Evol. Biol. (2006) [Pubmed]
  9. A role for CK2 in the Drosophila circadian oscillator. Akten, B., Jauch, E., Genova, G.K., Kim, E.Y., Edery, I., Raabe, T., Jackson, F.R. Nat. Neurosci. (2003) [Pubmed]
  10. Constructing a feedback loop with circadian clock molecules from the silkmoth, Antheraea pernyi. Chang, D.C., McWatters, H.G., Williams, J.A., Gotter, A.L., Levine, J.D., Reppert, S.M. J. Biol. Chem. (2003) [Pubmed]
  11. Casein kinase I in the Mammalian circadian clock. Eide, E.J., Kang, H., Crapo, S., Gallego, M., Virshup, D.M. Meth. Enzymol. (2005) [Pubmed]
  12. Genetics of the mammalian circadian system: Photic entrainment, circadian pacemaker mechanisms, and posttranslational regulation. Lowrey, P.L., Takahashi, J.S. Annu. Rev. Genet. (2000) [Pubmed]
  13. The Drosophila dCREB2 gene affects the circadian clock. Belvin, M.P., Zhou, H., Yin, J.C. Neuron (1999) [Pubmed]
  14. Detection of PERIOD/PAS-binding proteins from rat brain nuclear extracts by affinity chromatography. Qu, Z., Kako, K., Suzuki, S., Taniguchi, T., Ishida, N. Neurosci. Lett. (1999) [Pubmed]
  15. Analysis of period circadian expression in the Drosophila head by in situ hybridization. Rachidi, M., Lopes, C., Benichou, J.C., Rouyer, F. J. Neurogenet. (1997) [Pubmed]
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