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The circadian clock is the broadly conserved, protein-based, timekeeping mechanism that synchronizes biology to the Earth’s 24-h light-dark cycle. Studies of the mechanisms of circadian timekeeping have placed great focus on the role that individual protein-protein interactions play in the creation of the timekeeping loop. However, research has shown that clock proteins most commonly act as part of large macromolecular protein complexes to facilitate circadian control over physiology. The formation of these complexes has led to the large-scale study of the proteins that comprise these complexes, termed here “circadian interactomics.” Circadian interactomic studies of the macromolecular protein complexes that comprise the circadian clock have uncovered many basic principles of circadian timekeeping as well as mechanisms of circadian control over cellular physiology. In this review, we examine the wealth of knowledge accumulated using circadian interactomics approaches to investigate the macromolecular complexes of the core circadian clock, including insights into the core mechanisms that impart circadian timing and the clock’s regulation of many physiological processes. We examine data acquired from the investigation of the macromolecular complexes centered on both the activating and repressing arm of the circadian clock and from many circadian model organisms.
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Hello Darkness, My Old Friend: A Tutorial of Nanda-Hamner Protocols
Plants and animals use circadian and photoperiodic timekeeping mechanisms to respond to daily and seasonal changes in light:dark and appropriately coordinate their development. Although the mechanisms that may connect the circadian and photoperiodic clock are still unclear in many species, researchers have been using Nanda-Hamner protocols for decades to elucidate how seasonal time is measured and determine whether seasonal responses have a circadian basis in a given species. In this brief tutorial we describe how to design and interpret the results of Nanda-Hamner experiments, and provide suggestions on how to use both Nanda-Hamner protocols and modern molecular experiments to better understand the mechanisms of seasonal timekeeping.
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- PAR ID:
- 10251402
- Date Published:
- Journal Name:
- Journal of Biological Rhythms
- Volume:
- 36
- Issue:
- 3
- ISSN:
- 0748-7304
- Page Range / eLocation ID:
- 221 to 225
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract BackgroundCircadian (daily) timekeeping is essential to the survival of many organisms. An integral part of all circadian timekeeping systems is negative feedback between an activator and repressor. However, the role of this feedback varies widely between lower and higher organisms. ResultsHere, we study repression mechanisms in the cyanobacterial and eukaryotic clocks through mathematical modeling and systems analysis. We find a common mathematical model that describes the mechanism by which organisms generate rhythms; however, transcription’s role in this has diverged. In cyanobacteria, protein sequestration and phosphorylation generate and regulate rhythms while transcription regulation keeps proteins in proper stoichiometric balance. Based on recent experimental work, we propose a repressor phospholock mechanism that models the negative feedback through transcription in clocks of higher organisms. Interestingly, this model, when coupled with activator phosphorylation, allows for oscillations over a wide range of protein stoichiometries, thereby reconciling the negative feedback mechanism inNeurosporawith that in mammals and cyanobacteria. ConclusionsTaken together, these results paint a picture of how circadian timekeeping may have evolved.more » « less
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1177/0748730421998469
