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Circadian clock

Circadian Clock Mechanisms: – Circadian clock is a biochemical oscillator synchronized with solar time. – Most organisms have circadian clocks with a period close to […]

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Circadian Clock Mechanisms:
– Circadian clock is a biochemical oscillator synchronized with solar time.
– Most organisms have circadian clocks with a period close to 24 hours regulated by light.
– Central oscillator, input pathways, and output pathways are components of the circadian clock.
– Vertebrates have a master circadian clock in the suprachiasmatic nucleus (SCN) in the hypothalamus.
– Clocks in mammals, insects, fungi, and plants involve transcriptional feedback loops.
– Post-transcriptional and post-translational modifications like phosphorylation and methylation regulate circadian clocks.
– Circadian oscillators have a 24-hour period and are synchronized by external stimuli.
– Evolution of circadian clocks dates back billions of years, with non-transcriptional mechanisms observed in eukaryotes.
– Circadian regulation extends to various cellular processes and physiological phenomena in nature.

Gene Regulation in Circadian Clock:
– Genetic basis of circadian rhythms discovered in higher eukaryotes with core clock genes regulating feedback loops.
– Mammalian clock genes identified through knockout mutations and interlocking feedback loops.
– In insects and fungi, clock components regulate gene transcription and stability through feedback loops.
– Plant clock involves unique genes like TOC1, CCA1, and LHY with interlocking feedback loops.
– Bacterial circadian rhythms involve Kai proteins and ATP.
– Post-transcriptional and post-translational modifications govern circadian clock functioning.
– Regulatory networks involve phosphorylation, SUMOylation, and histone modifications.

Clock Genes and Modifiers:
– Genome-wide siRNA screens identify clock genes affecting rhythm amplitude.
– Protein interaction network analysis reveals associations with cellular pathways.
– Clock network utilizes compensatory mechanisms to maintain function.
– Dosage-dependent effects on oscillator function observed.
– Unidirectional paralog compensation mechanisms noted in clock gene regulation.

Circadian Rhythms in Different Organisms:
– Circadian rhythms are not universal, varying among organisms.
– Arctic, migratory, and dark biosphere organisms exhibit unique circadian rhythms.
– Clock mechanisms in different organisms show similarities in transcriptional feedback loops.
– Circadian clocks in red blood cells, cyanobacteria, and other eukaryotes demonstrate persistence without transcription.
– Circadian rhythms regulate specific physiological processes in different organisms.

Chromatin Landscape and RNA Processing:
– Transcriptional architecture and chromatin landscape influence the core circadian clock in mammals.
– RNA processing, including mRNA polyadenylation and methylation, affects circadian clock speed.
– Rhythmic oxygen levels reset circadian clocks through HIF1α.
– Circadian clocks impact lung health and disease through their regulatory mechanisms.
– Post-translational modifications regulate the circadian clock’s ticking in various organisms.

Circadian clock (Wikipedia)

A circadian clock, or circadian oscillator, also known as one’s internal alarm clock is a biochemical oscillator that cycles with a stable phase and is synchronized with solar time.

Such a clock's in vivo period is necessarily almost exactly 24 hours (the earth's current solar day). In most living organisms, internally synchronized circadian clocks make it possible for the organism to anticipate daily environmental changes corresponding with the day–night cycle and adjust its biology and behavior accordingly.

The term circadian derives from the Latin circa (about) dies (a day), since when taken away from external cues (such as environmental light), they do not run to exactly 24 hours. Clocks in humans in a lab in constant low light, for example, will average about 24.2 hours per day, rather than 24 hours exactly.

The normal body clock oscillates with an endogenous period of exactly 24 hours, it entrains, when it receives sufficient daily corrective signals from the environment, primarily daylight and darkness. Circadian clocks are the central mechanisms that drive circadian rhythms. They consist of three major components:

  • a central biochemical oscillator with a period of about 24 hours that keeps time;
  • a series of input pathways to this central oscillator to allow entrainment of the clock;
  • a series of output pathways tied to distinct phases of the oscillator that regulate overt rhythms in biochemistry, physiology, and behavior throughout an organism.

The clock is reset as an organism senses environmental time cues of which the primary one is light. Circadian oscillators are ubiquitous in tissues of the body where they are synchronized by both endogenous and external signals to regulate transcriptional activity throughout the day in a tissue-specific manner. The circadian clock is intertwined with most cellular metabolic processes and it is affected by organism aging. The basic molecular mechanisms of the biological clock have been defined in vertebrate species, Drosophila melanogaster, plants, fungi, bacteria, and presumably also in Archaea.

In 2017, the Nobel Prize in Physiology or Medicine was awarded to Jeffrey C. Hall, Michael Rosbash and Michael W. Young "for their discoveries of molecular mechanisms controlling the circadian rhythm" in fruit flies.

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