ArticleThe Journal of biological chemistry2012
Identification of a novel cryptochrome differentiating domain required for feedback repression in circadian clock function.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 75 citations in OpenAlex.
- Targeting Cryptochromes in Chronic Diseases.Cell biology international · 2025Review
- 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
- Circadian rhythm regulates the function of immune cells and participates in the development of tumors.Cell death discovery · 2024Review
- A structural decryption of cryptochromes.Frontiers in chemistry · 2024Review
- Functional characterization of the CRY2 circadian clock component variant p.Ser420Phe revealed a new degradation pathway for CRY2.The Journal of biological chemistry · 2023Article
- Discovery of a small molecule that selectively destabilizes Cryptochrome 1 and enhances life span in p53 knockout mice.Nature communications · 2022Article
- The secondary pocket of cryptochrome 2 is important for the regulation of its stability and localization.The Journal of biological chemistry · 2022Article
- Structural and Chemical Biology Approaches Reveal Isoform-Selective Mechanisms of Ligand Interactions in Mammalian Cryptochromes.Frontiers in physiology · 2022Review
- The molecular clock gene cryptochrome 1 (Cephalalgia : an international journal of headache · 2021Article
- NF-κB modifies the mammalian circadian clock through interaction with the core clock protein BMAL1.PLoS genetics · 2021Article
- Live-cell imaging of circadian clock protein dynamics in CRISPR-generated knock-in cells.Nature communications · 2021Article
- Cryptochromes and the Circadian Clock: The Story of a Very Complex Relationship in a Spinning World.Genes · 2021Review
- Structural insights into photoactivation of plant Cryptochrome-2.Communications biology · 2021Article
- The Arg-293 of Cryptochrome1 is responsible for the allosteric regulation of CLOCK-CRY1 binding in circadian rhythm.The Journal of biological chemistry · 2020Article
- The tail of cryptochromes: an intrinsically disordered cog within the mammalian circadian clock.Cell communication and signaling : CCS · 2020Review
- Intrinsic disorder is an essential characteristic of components in the conserved circadian circuit.Cell communication and signaling : CCS · 2020Review
- The human CRY1 tail controls circadian timing by regulating its association with CLOCK:BMAL1.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Cryptochromes Suppress HIF1α in Muscles.iScience · 2020Article
- Vulnerability to helpless behavior is regulated by the circadian clock component CRYPTOCHROME in the mouse nucleus accumbens.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Orchestration of Circadian Timing by Macromolecular Protein Assemblies.Journal of molecular biology · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Circadian clocks in mammals are based on a negative feedback loop in which transcriptional repression by the cryptochromes, CRY1 and CRY2, lies at the heart of the mechanism. Despite similarities in sequence, domain structure, and biochemical activity, they play distinct roles in clock function. However, detailed biochemical studies have not been straightforward and Cry function has not been examined in real clock cells using kinetic measurements. In this study, we demonstrate, through cell-based genetic complementation and real-time molecular recording, that Cry1 alone is able to maintain cell-autonomous circadian rhythms, whereas Cry2 cannot. Using this novel functional assay, we identify a cryptochrome differentiating α-helical domain within the photolyase homology region (PHR) of CRY1, designated as CRY1-PHR(313-426), that is required for clock function and distinguishes CRY1 from CRY2. Contrary to speculation, the divergent carboxyl-terminal tail domain (CTD) is dispensable, but serves to modulate rhythm amplitude and period length. Finally, we identify the biochemical basis of their distinct function; CRY1 is a much more potent transcriptional repressor than CRY2, and the strength of repression by various forms of CRY proteins significantly correlates with rhythm amplitude. Taken together, our results demonstrate that CRY1-PHR(313-426), not the divergent CTD, is critical for clock function. These findings provide novel insights into the evolution of the diverse functions of the photolyase/cryptochrome family of flavoproteins and offer new opportunities for mechanistic studies of CRY function.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.