ArticleProceedings of the National Academy of Sciences of the United States of America2020
The human CRY1 tail controls circadian timing by regulating its association with CLOCK:BMAL1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 69 citations in OpenAlex.
- The Human Circadian Clock Protein Cryptochrome-1 Responds to Photochemistry by Conformational Changes.Journal of the American Chemical Society · 2026Article
- Breaking the Efflux Barrier: P-Glycoprotein and Emerging Strategies to Overcome Multidrug Resistance in Cancer.Cancers · 2026Review
- The CLOCK-BMAL1 complex in circadian regulation: structure, mechanisms, and therapeutic targeting.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- DHHC3-dependent S-Acylation of CRY1 regulates its subcellular localization and repressor function in the circadian clock.bioRxiv : the preprint server for biology · 2026Article
- Review
- Disordered but rhythmic-the role of intrinsic protein disorder in eukaryotic circadian timing.FEBS letters · 2026Review
- Altered peripheral CRY1 gene expression may contribute to both organic and functional gastrointestinal disease.Experimental physiology · 2026Article
- Conserved structural motifs in PAS, LOV, and CRY proteins regulate circadian rhythms and are therapeutic targets.FEBS letters · 2026Review
- Biochemical mechanism of the mammalian circadian clock.FEBS letters · 2026Review
- Genome-wide characterization of the wheat cryptochrome/photolyase family identifies TaCRY1b as a lamina-joint-associated protein interacting with TaLG2 and TaLG2L.Frontiers in plant science · 2026Article
- Senescence-circadian interplay stratifies patient prognosis and reveals immune remodeling heterogeneity in colorectal cancer.Frontiers in immunology · 2026Article
- Targeting Cryptochromes in Chronic Diseases.Cell biology international · 2025Review
- A conserved chronobiological complex times C. elegans development.The EMBO journal · 2025Article
- Tandem association of CLOCK:BMAL1 complexes on DNA enables recruitment of CBP/p300 through multivalent interactions.bioRxiv : the preprint server for biology · 2025Article
- CRY1 Lysine 151 Regulates Circadian Rhythms Through Ubiquitination-Independent Protein Interactions.International journal of molecular sciences · 2025Article
- Full-Length Cryptochrome 1 in the Outer Segments of the Retinal Blue Cone Photoreceptors in Humans and Great Apes Suggests a Role Beyond Transcriptional Repression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Evolution of canonical circadian clock genes underlies unique sleep strategies of marine mammals for secondary aquatic adaptation.PLoS genetics · 2025Article
- Research progress on the mutual regulatory mechanism of circadian clock genes and autophagy.Frontiers in cell and developmental biology · 2025Review
- Chrono-tailored drug delivery systems: recent advances and future directions.Drug delivery and translational research · 2024Review
- Crosstalk between Circadian Rhythm Dysregulation and Tumorigenesis, Tumor Metabolism and Tumor Immune Response.Aging and disease · 2024Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Circadian rhythms are generated by interlocked transcription-translation feedback loops that establish cell-autonomous biological timing of ∼24 h. Mutations in core clock genes that alter their stability or affinity for one another lead to changes in circadian period. The human CRY1Δ11 mutant lengthens circadian period to cause delayed sleep phase disorder (DSPD), characterized by a very late onset of sleep. CRY1 is a repressor that binds to the transcription factor CLOCK:BMAL1 to inhibit its activity and close the core feedback loop. We previously showed how the PHR (photolyase homology region) domain of CRY1 interacts with distinct sites on CLOCK and BMAL1 to sequester the transactivation domain from coactivators. However, the Δ11 variant alters an intrinsically disordered tail in CRY1 downstream of the PHR. We show here that the CRY1 tail, and in particular the region encoded by exon 11, modulates the affinity of the PHR domain for CLOCK:BMAL1. The PHR-binding epitope in exon 11 is necessary and sufficient to disrupt the interaction between CRY1 and the subunit CLOCK. Moreover, PHR-tail interactions are conserved in the paralog CRY2 and reduced when either CRY is bound to the circadian corepressor PERIOD2. Discovery of this autoregulatory role for the mammalian CRY1 tail and conservation of PHR-tail interactions in both mammalian cryptochromes highlights functional conservation with plant and insect cryptochromes, which also utilize PHR-tail interactions to reversibly control their activity.
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