4 From Genetics to Molecular Oscillations: The Circadian Clock in Neurospora crassa

Jankowski, Meaghan S.; Chase, Zachary A.; Hurley, Jennifer M.

doi:10.1007/978-3-030-49924-2_4

Cited by 2 publications

(3 citation statements)

References 188 publications

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“…This primed Neurospora’s readiness as a model for circadian research when Pittendrigh described the visual phenotypic clock output of conidial formation of Neurospora growing on race tubes (Beadle and Tatum, 1941; Pittendrigh et al, 1959). Since then, Neurospora has contributed greatly to the elucidation of the genetic and biochemical mechanisms of eukaryotic clocks, as well as to the fields of recombination, gene action, and cell growth in eukaryotic cells (Loros, 1998; Fuller et al, 2014; Roche et al, 2014; Jankowski et al, 2020). In Neurospora , the core negative-arm protein is FREQUENCY (FRQ; Dunlap and Loros, 2004; Cha et al, 2015; Pelham et al, 2018).…”

Section: Macromolecular Complexes That Coalesce Around the Negative Arm Of The Circadian Clockmentioning

confidence: 99%

“…Liu and Bell-Pedersen, 2006; Baker et al, 2012; Beckwith and Yanovsky, 2014; Hurley et al, 2014; Sancar et al, 2015). The WCC is also the conduit through which environmental stimuli, for example, light and glucose levels, are integrated into the circadian circuit (Jankowski et al, 2020).…”

Section: Macromolecular Complexes That Coalesce Around the Positive Arm Of The Circadian Clockmentioning

confidence: 99%

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Circadian Interactomics: How Research Into Protein-Protein Interactions Beyond the Core Clock Has Influenced the Model of Circadian Timekeeping

Mosier

Hurley

2021

J Biol Rhythms

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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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Section: Macromolecular Complexes That Coalesce Around the Negative Arm Of The Circadian Clockmentioning

confidence: 99%

Section: Macromolecular Complexes That Coalesce Around the Positive Arm Of The Circadian Clockmentioning

confidence: 99%

Circadian Interactomics: How Research Into Protein-Protein Interactions Beyond the Core Clock Has Influenced the Model of Circadian Timekeeping

Mosier

Hurley

2021

J Biol Rhythms

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“…Circadian clocks have evolved as an adaptive mechanism to anticipate daily environmental changes and are recognized as an important regulator of the cellular environment (Dunlap and Loros, 2017; Jankowski et al, 2020; Partch, 2020). The rhythms generated by these clocks are widely conserved amongst eukaryotes and their dysregulation leads to an increase in disease in humans (Dunlap and Loros, 2017; Evans and Davidson, 2013; Musiek and Holtzman, 2016; Shostak, 2017).…”

Section: Introductionmentioning

confidence: 99%

The formation of a fuzzy complex in the negative arm regulates the robustness of the circadian clock

Jankowski

Griffith

Shastry

et al. 2022

Preprint

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The circadian clock times cellular processes to the day/night cycle via a Transcription-Translation negative Feedback Loop (TTFL). However, a mechanistic understanding of the negative arm in both the timing of the TTFL and its control of output is lacking. We posited that the formation of negative-arm protein complexes was fundamental to clock regulation stemming from the negative arm. Using a modified peptide microarray approach termed Linear motif discovery using rational design (LOCATE), we characterized the interaction of the disordered negative-arm clock protein FREQUENCY to its partner protein FREQUENCY-Interacting RNA helicase. LOCATE identified a specific Short Linear Motif (SLiM) and interaction hotspot as well as positively charged islands that mediate electrostatic interactions, suggesting a model where negative arm proteins form a fuzzy complex essential for clock timing and robustness. Further analysis revealed that the positively charged islands were an evolutionarily conserved feature in higher eukaryotes and contributed to proper clock function.

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4 From Genetics to Molecular Oscillations: The Circadian Clock in Neurospora crassa

Cited by 2 publications

References 188 publications

Circadian Interactomics: How Research Into Protein-Protein Interactions Beyond the Core Clock Has Influenced the Model of Circadian Timekeeping

Circadian Interactomics: How Research Into Protein-Protein Interactions Beyond the Core Clock Has Influenced the Model of Circadian Timekeeping

The formation of a fuzzy complex in the negative arm regulates the robustness of the circadian clock

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