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Gene Review

cyc  -  cycle

Drosophila melanogaster

Synonyms: BMAL1, Bmal1, Brain and muscle ARNT-like 1, CG8727, CYC, ...
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High impact information on cyc

  • The molecular circadian phenotype of homozygous cyc flies is like homozygous Clk flies presented in the accompanying paper: mutant flies have little or no transcription of the per and tim genes [1].
  • Cloning of the gene indicates that it also encodes a bHLH-PAS transcription factor and is a Drosophila homolog of the human protein BMAL1. cyc is a nonsense mutation, consistent with its strong loss-of-function phenotype [1].
  • Functional Differentiation of SWI/SNF Remodelers in Transcription and Cell Cycle Control [2].
  • 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 [3].
  • A robust circadian rhythm of rat BMAL1 expression was detected by in situ hybridization in the suprachiasmatic nucleus (SCN), the site of the circadian clock, with the highest level at the subjective night [4].

Biological context of cyc


Anatomical context of cyc

  • Antiphase circadian expression between BMAL1 and period homologue mRNA in the suprachiasmatic nucleus and peripheral tissues of rats [8].
  • Transcripts encoded by the seven known mammalian canonical circadian genes (Per1-3, Cry1-2, Bmal1 and Clock), plus the mammalian genetic homologue of the Drosophila canonical gene Timeless, were detected in the uteri and oviducts taken from mice on days 1-4 of pregnancy and in unfertilized oocytes [9].

Associations of cyc with chemical compounds

  • The Drosophila CLOCK (dCLOCK) and CYCLE (CYC) (also referred to as dBMAL1) proteins are members of the basic helix-loop-helix PAS (PER-ARNT-SIM) superfamily of transcription factors and are required for high-level expression of the circadian clock genes period (per) and timeless (tim) [10].

Enzymatic interactions of cyc

  • CKI also phosphorylates and partially activates the transcription factor BMAL1 [11].

Other interactions of cyc

  • Per and Tim then associate, translocate to the nucleus, and repress the activity of Clk and Cyc [12].

Analytical, diagnostic and therapeutic context of cyc


  1. CYCLE is a second bHLH-PAS clock protein essential for circadian rhythmicity and transcription of Drosophila period and timeless. Rutila, J.E., Suri, V., Le, M., So, W.V., Rosbash, M., Hall, J.C. Cell (1998) [Pubmed]
  2. Functional Differentiation of SWI/SNF Remodelers in Transcription and Cell Cycle Control. Moshkin, Y.M., Mohrmann, L., van Ijcken, W.F., Verrijzer, C.P. Mol. Cell. Biol. (2007) [Pubmed]
  3. 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]
  4. Circadian oscillation of BMAL1, a partner of a mammalian clock gene Clock, in rat suprachiasmatic nucleus. Honma, S., Ikeda, M., Abe, H., Tanahashi, Y., Namihira, M., Honma, K., Nomura, M. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  5. Closing the circadian loop: CLOCK-induced transcription of its own inhibitors per and tim. Darlington, T.K., Wager-Smith, K., Ceriani, M.F., Staknis, D., Gekakis, N., Steeves, T.D., Weitz, C.J., Takahashi, J.S., Kay, S.A. Science (1998) [Pubmed]
  6. Vinegar flies turn to porto for cell division cycle meeting. Richardson, H.E. Dev. Cell (2006) [Pubmed]
  7. A cyclin built for two. New Approaches to Understanding Cell Cycle Regulation sponsored by the Molecular Biology and Molecular Cytology Study Sections, Division of Research Grants, National Institutes of Health Bethesda, MD, USA, October 11, 1989. Cross, S.L. New Biol. (1990) [Pubmed]
  8. Antiphase circadian expression between BMAL1 and period homologue mRNA in the suprachiasmatic nucleus and peripheral tissues of rats. Oishi, K., Sakamoto, K., Okada, T., Nagase, T., Ishida, N. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  9. Circadian clockwork genes are expressed in the reproductive tract and conceptus of the early pregnant mouse. Johnson, M.H., Lim, A., Fernando, D., Day, M.L. Reprod. Biomed. Online (2002) [Pubmed]
  10. PER and TIM inhibit the DNA binding activity of a Drosophila CLOCK-CYC/dBMAL1 heterodimer without disrupting formation of the heterodimer: a basis for circadian transcription. Lee, C., Bae, K., Edery, I. Mol. Cell. Biol. (1999) [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. A role for casein kinase 2alpha in the Drosophila circadian clock. Lin, J.M., Kilman, V.L., Keegan, K., Paddock, B., Emery-Le, M., Rosbash, M., Allada, R. Nature (2002) [Pubmed]
  13. Mutations of the PH domain of protein kinase B (PKB/AKT) are absent in human epidermal skin tumors. Waldmann, V., Wacker, J. Dermatology (Basel) (2001) [Pubmed]
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