Circadian Rhythms

Abstract

Daily (circadian) rhythms of behaviour and physiology are prevalent in organisms ranging from cyanobacteria to humans. These rhythms are not simply responses to environmental cues, but are driven by endogenous cellular clocks. Circadian clocks are synchronised to daily environmental cycles to produce 24 h molecular oscillations, which in turn drive rhythmic outputs. The mechanisms that produce circadian rhythms have been elucidated in a number of species, and several features of this system are common to most or all rhythmic organisms. Among animals, the molecular components that make up the circadian clock system are highly conserved, and mutations in human clock genes are associated with specific sleep disorders. Circadian rhythms defects in humans are also associated with other serious conditions such as mental health conditions and metabolic disorders.

Key Concepts:

  • Circadian rhythms are found in a wide range of organisms.

  • Circadian clocks utilise transcriptional feedback loops and post‐translational modifications.

  • Circadian clocks are located in most or all tissues in humans.

  • Circadian clocks control cell function and physiology through rhythmic gene expression.

Keywords: circadian clock; rhythms; environmental cycles; entrainment; pacemaker; suprachiasmatic nucleus; Drosophila

Figure 1.

Circadian clocks typically consist of transcriptional feedback loops and post‐translational modifications. Depiction of the molecular circadian clock in Drosophila melanogaster. The CLK‐CYC heterodimeric transcription factor upregulates transcription of target genes through binding E‐box regulatory sequences. CLK‐CYC target genes per and tim encode proteins that feedback to inhibit CLK‐CYC activity, thus repressing their own transcription. In a second feedback loop, CLK‐CYC upregulates vri and Pdp1, which encode transcription factors that regulate clk transcription. A third loop involves the CLK‐CYC target cwo, which likely represses E‐box transcription at specific times of day. Kinases (CK2, DBT and SGG) and phosphatases (PP1 and PP2A) regulate the stability and/or subcellular distribution of clock proteins to promote ∼24 h molecular oscillations, whereas the ubiquitin ligase SLIMB mediates degradation of hyperphosphorylated PER and TIM. The CRY photoreceptor binds to TIM in the presence of blue light, leading to degradation of both proteins and resetting the clock.

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Further Reading

Albrecht U (ed.) (2010) The Circadian Clock. New York: Springer.

Dunlap JC, Loros JJ and DeCoursey PJ (eds) (2009) Chronobiology: Biological Timekeeping. Sunderland, MA: Sinauer Associates.

Foster RG and Kreitzman L (2005) Rhythms of Life: The Biological Clocks that Control the Daily Lives of Every Living Thing. New Haven, CT: Yale University Press.

Sehgal A (ed.) (2004) Molecular Biology of Circadian Rhythms. Hoboken, NJ: John Wiley & Sons, Inc.

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Lear, Bridget C, and Allada, Ravi(Jan 2012) Circadian Rhythms. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000040.pub2]