ArticleProceedings of the National Academy of Sciences of the United States of America2016
Early doors (Edo) mutant mouse reveals the importance of period 2 (PER2) PAS domain structure for circadian pacemaking.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- Selection on PER2 Phosphorylation Regulation Underlies Atypical Mammalian Circadian Rhythms.Ecology and evolution · 2026Article
- Time matters: circadian genetics and the molecular logic of human health and disease.Nature reviews. Genetics · 2026Review
- PER2 reprograms intracellular cholesterol synthesis to inhibit oral squamous cell carcinoma and the chronotherapeutic efficacy of simvastatin.Cell death discovery · 2026Article
- PER2 interaction with HSP70 promotes cuproptosis in oral squamous carcinoma cells by decreasing AKT stability.Cell death & disease · 2025Article
- The role of circadian rhythm regulator PERs in oxidative stress, immunity, and cancer development.Cell communication and signaling : CCS · 2025Review
- Protein-adaptive differential scanning fluorimetry using conformationally responsive dyes.Nature biotechnology · 2025Article
- PERfect Day: reversible and dose-dependent control of circadian time-keeping in the mouse suprachiasmatic nucleus by translational switching of PERIOD2 protein expression.The European journal of neuroscience · 2024Article
- PAS Dimerization at the Nexus of the Mammalian Circadian Clock.Journal of molecular biology · 2024Review
- Biological clock regulation by theFrontiers in cell and developmental biology · 2024Review
- Metabolic and chemical architecture of the mammalian circadian clock.Cell chemical biology · 2023Review
- Time to target the circadian clock for drug discovery.Trends in biochemical sciences · 2022Review
- Biochemical mechanisms of period control within the mammalian circadian clock.Seminars in cell & developmental biology · 2022Review
- Cryptochrome proteins regulate the circadian intracellular behavior and localization of PER2 in mouse suprachiasmatic nucleus neurons.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Disrupted-in-schizophrenia 1 enhances the quality of circadian rhythm by stabilizing BMAL1.Translational psychiatry · 2021Article
- 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
- A role for the clock period circadian regulator 2 gene in regulating the clock gene network in human oral squamous cell carcinoma cells.Oncology letters · 2018Article
- Whole exome sequencing reveals a functional mutation in the GAIN domain of the Bai2 receptor underlying a forward mutagenesis hyperactivity QTL.Mammalian genome : official journal of the International Mammalian Genome Society · 2017Article
- Inhibition of expression of the circadian clock gene Period causes metabolic abnormalities including repression of glycometabolism in Bombyx mori cells.Scientific reports · 2017Article
- Regulating the Suprachiasmatic Nucleus (SCN) Circadian Clockwork: Interplay between Cell-Autonomous and Circuit-Level Mechanisms.Cold Spring Harbor perspectives in biology · 2017Review
- The intricate dance of post-translational modifications in the rhythm of life.Nature structural & molecular biology · 2016Review
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
The suprachiasmatic nucleus (SCN) defines 24 h of time via a transcriptional/posttranslational feedback loop in which transactivation of Per (period) and Cry (cryptochrome) genes by BMAL1-CLOCK complexes is suppressed by PER-CRY complexes. The molecular/structural basis of how circadian protein complexes function is poorly understood. We describe a novel N-ethyl-N-nitrosourea (ENU)-induced mutation, early doors (Edo), in the PER-ARNT-SIM (PAS) domain dimerization region of period 2 (PER2) (I324N) that accelerates the circadian clock of Per2(Edo/Edo) mice by 1.5 h. Structural and biophysical analyses revealed that Edo alters the packing of the highly conserved interdomain linker of the PER2 PAS core such that, although PER2(Edo) complexes with clock proteins, its vulnerability to degradation mediated by casein kinase 1ε (CSNK1E) is increased. The functional relevance of this mutation is revealed by the ultrashort (<19 h) but robust circadian rhythms in Per2(Edo/Edo); Csnk1e(Tau/Tau) mice and the SCN. These periods are unprecedented in mice. Thus, Per2(Edo) reveals a direct causal link between the molecular structure of the PER2 PAS core and the pace of SCN circadian timekeeping.
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