Animal Cryptochromes: Divergent Roles in Light Perception, Circadian Timekeeping and Beyond

Michael, Alicia K.; Fribourgh, Jennifer L.; Gelder, Russell N. Van; Partch, Carrie L.

doi:10.1111/php.12677

Cited by 84 publications

(82 citation statements)

References 141 publications

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“…Animal cryptochromes are thought to have evolved from ancestral photolyases associated with light-dependent DNA repair (Mei and Dvornyk, 2015) and now include regulators of circadian rhythms (Özturk et al, 2007; Michael et al, 2017). Animal cryptochromes can be photoreceptive (PCRY), providing direct light input into the circadian clock, or non-photoreceptive (NPCRY), possibly acting as transcriptional repressors of clock genes.…”

Section: Discussionmentioning

confidence: 99%

“…PERIOD and NPCRY then serve as the negative inhibitors of the clock (Reppert and Weaver, 2002; Lowrey and Takahashi, 2004). NPCRY is closely related to a protostome NPCRY, found in many invertebrates, but not present in Drosophila (Lin and Todo, 2005; Özturk, 2016; Michael et al, 2017). A TIMELESS protein was initially identified in mammals (Koike et al, 1998; Sangoram et al, 1998; Takumi et al, 1999), but this is now believed to actually be an ortholog of TIMEOUT (Li et al, 2016), which is a paralog of TIMELESS.…”

Section: Introductionmentioning

confidence: 99%

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Sequences of Circadian Clock Proteins in the Nudibranch Molluscs Hermissenda crassicornis, Melibe leonina, and Tritonia diomedea

Cook

Gruen

Morris

et al. 2018

The Biological Bulletin

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While much is known about the genes and proteins that make up the circadian clocks in vertebrates and several arthropod species, much less is known about the clock genes in many other invertebrates, including nudibranchs. The goal of this project was to identify the RNA and protein products of putative clock genes in the central nervous system of three nudibranchs, Hermissenda crassicornis, Melibe leonina, and Tritonia diomedea. Using previously published transcriptomes (Hermissenda and Tritonia) and a new transcriptome (Melibe), we identified nudibranch orthologs for the products of five canonical clock genes: brain and muscle aryl hydrocarbon receptor nuclear translocator like protein 1, circadian locomotor output cycles kaput, non-photoreceptive cryptochrome, period, and timeless. Additionally, orthologous sequences for the products of five related genes—aryl hydrocarbon receptor nuclear translocator like, photoreceptive cryptochrome, cryptochrome DASH, 6-4 photolyase, and timeout—were determined. Phylogenetic analyses confirmed that the nudibranch proteins were most closely related to known orthologs in related invertebrates, such as oysters and annelids. In general, the nudibranch clock proteins shared greater sequence similarity with Mus musculus orthologs than Drosophila melanogaster orthologs, which is consistent with the closer phylogenetic relationships recovered between lophotrochozoan and vertebrate orthologs. The suite of clock-related genes in nudibranchs includes both photoreceptive and non-photoreceptive cryptochromes, as well as timeout and possibly timeless. Therefore, the nudibranch clock may resemble the one exhibited in mammals, or possibly even in non-drosopholid insects and oysters. The latter would be evidence supporting this as the ancestral clock for bilaterians.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sequences of Circadian Clock Proteins in the Nudibranch Molluscs Hermissenda crassicornis, Melibe leonina, and Tritonia diomedea

Cook

Gruen

Morris

et al. 2018

The Biological Bulletin

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“…Although it has been nearly two decades since the identification of cryptochromes and discovery of their essential role in circadian rhythms, it is still not clear how cryptochromes interact with CLOCK:BMAL1 to inhibit their activity and close the transcription-translation feedback loop of the clock (33). Probing the molecular details of transcription factor-regulator interactions in the clock is important, because they control 24-h timekeeping and generate a vast network of clock-controlled genes that confer circadian timing to physiology and behavior.…”

Section: Discussionmentioning

confidence: 99%

Formation of a repressive complex in the mammalian circadian clock is mediated by the secondary pocket of CRY1

Michael

Fribourgh

Chelliah

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The basic helix–loop–helix PAS domain (bHLH-PAS) transcription factor CLOCK:BMAL1 (brain and muscle Arnt-like protein 1) sits at the core of the mammalian circadian transcription/translation feedback loop. Precise control of CLOCK:BMAL1 activity by coactivators and repressors establishes the ∼24-h periodicity of gene expression. Formation of a repressive complex, defined by the core clock proteins cryptochrome 1 (CRY1):CLOCK:BMAL1, plays an important role controlling the switch from repression to activation each day. Here we show that CRY1 binds directly to the PAS domain core of CLOCK:BMAL1, driven primarily by interaction with the CLOCK PAS-B domain. Integrative modeling and solution X-ray scattering studies unambiguously position a key loop of the CLOCK PAS-B domain in the secondary pocket of CRY1, analogous to the antenna chromophore-binding pocket of photolyase. CRY1 docks onto the transcription factor alongside the PAS domains, extending above the DNA-binding bHLH domain. Single point mutations at the interface on either CRY1 or CLOCK disrupt formation of the ternary complex, highlighting the importance of this interface for direct regulation of CLOCK:BMAL1 activity by CRY1.

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“…The RAD23 and RAD14 proteins bind damaged DNA, reminiscent of a documented clock function in mammals and the green yeast, Chlamydomonas 70,71 . CNM67, a hub with 16 connections in the yeast PREMONition network, is involved in spindle body formation, a connection to the cell cycle machinery, linking this network to observations of gating of cell division 72,73 .…”

Section: The Yeast Premonition Network In Generalmentioning

confidence: 99%

PREMONition: An algorithm for predicting the circadian clock-regulated molecular network

Bosman

Eelderink-Chen

Laing

et al. 2018

Preprint

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words)A transcriptional feedback loop is central to clock function in animals, plants and fungi. The clock genes involved in its regulation are specific to -and highly conserved within -the kingdoms of life. However, other shared clock mechanisms, such as phosphorylation, are mediated by proteins found broadly among living organisms, performing functions in many cellular sub-systems. Use of homology to directly infer involvement/association with the clock mechanism in new, developing model systems, is therefore of limited use. Here we describe the approach PREMONition, PREdicting Molecular Networks, that uses functional relationships to predict molecular circadian clock associations. PREMONition is based on the incorporation of proteins encoded by known clock genes (when available), rhythmically expressed clockcontrolled genes and non-rhythmically expressed but interacting genes into a cohesive network.After tuning PREMONition on the networks derived for human, fly and fungal circadian clocks, we deployed the approach to predict a molecular clock network for Saccharomyces cerevisiae, for which there are no readily-identifiable clock gene homologs. The predicted network was validated using gene expression data and a growth assay for sensitivity to light, a zeitgeber of circadian clocks of most organisms. PREMONition may be used to identify candidate clockregulated processes and thus candidate clock genes in other organisms.Keywords: circadian clock / interactome / S. cerevisiae / network / circadian rhythm the absence of identified clock genes. For instance, Neurospora crassa shows free-running rhythms and circadian entrainment without the clock gene frequency 3,4 and rhythms in the redox state of peroxiredoxin persist in many model genetic systems in the absence of transcription or of clock genes 5 . Paracrine signaling can sustain circadian rhythms in pacemaker (neuronal) tissue that lacks clock genes and displays no endogenous rhythm 6 . One interpretation of this is that feedback integral to circadian clocks spans multiple molecular 'levels', from transcription to metabolism. We conjecture that this multi-level response can be captured through functional relationships, referred to as functional interactions. We know of no models that explicitly attempt to integrate these different levels to more fully describe the mechanisms of the circadian clock. Here, we describe the method PREMONition, PREdicting MOlecular Networks, to construct multi-level (functional) molecular clock networks using publicly available datasets and bioinformatics tools. After tuning the method on clock genetic model systems, we deployed PREMONition to predict a molecular clock network in S. cerevisiae, an experimental system with a circadian phenotype that is not suited to genetic screens 7 . We validated the results of the yeast experiment in silico and in vivo. Methods like PREMONition, that span multiple levels in the cell, are essential to developing integrative models of complex biological processes. Results PREMONition applied to mod...

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Animal Cryptochromes: Divergent Roles in Light Perception, Circadian Timekeeping and Beyond

Cited by 84 publications

References 141 publications

Sequences of Circadian Clock Proteins in the Nudibranch Molluscs Hermissenda crassicornis, Melibe leonina, and Tritonia diomedea

Sequences of Circadian Clock Proteins in the Nudibranch Molluscs Hermissenda crassicornis, Melibe leonina, and Tritonia diomedea

Formation of a repressive complex in the mammalian circadian clock is mediated by the secondary pocket of CRY1

PREMONition: An algorithm for predicting the circadian clock-regulated molecular network

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