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CRYPTOCHROMES confer robustness, not rhythmicity, to circadian timekeeping.
Putker, Marrit; Wong, David C S; Seinkmane, Estere; Rzechorzek, Nina M; Zeng, Aiwei; Hoyle, Nathaniel P; Chesham, Johanna E; Edwards, Mathew D; Feeney, Kevin A; Fischer, Robin; Peschel, Nicolai; Chen, Ko-Fan; Vanden Oever, Michael; Edgar, Rachel S; Selby, Christopher P; Sancar, Aziz; O'Neill, John S.
Afiliación
  • Putker M; MRC Laboratory of Molecular Biology, Cambridge, UK.
  • Wong DCS; MRC Laboratory of Molecular Biology, Cambridge, UK.
  • Seinkmane E; MRC Laboratory of Molecular Biology, Cambridge, UK.
  • Rzechorzek NM; MRC Laboratory of Molecular Biology, Cambridge, UK.
  • Zeng A; MRC Laboratory of Molecular Biology, Cambridge, UK.
  • Hoyle NP; MRC Laboratory of Molecular Biology, Cambridge, UK.
  • Chesham JE; MRC Laboratory of Molecular Biology, Cambridge, UK.
  • Edwards MD; MRC Laboratory of Molecular Biology, Cambridge, UK.
  • Feeney KA; MRC Laboratory of Molecular Biology, Cambridge, UK.
  • Fischer R; Biozentrum Universität, Würzburg, Germany.
  • Peschel N; Biozentrum Universität, Würzburg, Germany.
  • Chen KF; Institute of Neurology, University College London, London, UK.
  • Vanden Oever M; Faculty of Medicine, Imperial College London, London, UK.
  • Edgar RS; Faculty of Medicine, Imperial College London, London, UK.
  • Selby CP; Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
  • Sancar A; Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
  • O'Neill JS; MRC Laboratory of Molecular Biology, Cambridge, UK.
EMBO J ; 40(7): e106745, 2021 04 01.
Article en En | MEDLINE | ID: mdl-33491228
Circadian rhythms are a pervasive property of mammalian cells, tissues and behaviour, ensuring physiological adaptation to solar time. Models of cellular timekeeping revolve around transcriptional feedback repression, whereby CLOCK and BMAL1 activate the expression of PERIOD (PER) and CRYPTOCHROME (CRY), which in turn repress CLOCK/BMAL1 activity. CRY proteins are therefore considered essential components of the cellular clock mechanism, supported by behavioural arrhythmicity of CRY-deficient (CKO) mice under constant conditions. Challenging this interpretation, we find locomotor rhythms in adult CKO mice under specific environmental conditions and circadian rhythms in cellular PER2 levels when CRY is absent. CRY-less oscillations are variable in their expression and have shorter periods than wild-type controls. Importantly, we find classic circadian hallmarks such as temperature compensation and period determination by CK1δ/ε activity to be maintained. In the absence of CRY-mediated feedback repression and rhythmic Per2 transcription, PER2 protein rhythms are sustained for several cycles, accompanied by circadian variation in protein stability. We suggest that, whereas circadian transcriptional feedback imparts robustness and functionality onto biological clocks, the core timekeeping mechanism is post-translational.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ritmo Circadiano / Criptocromos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: EMBO J Año: 2021 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ritmo Circadiano / Criptocromos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: EMBO J Año: 2021 Tipo del documento: Article Pais de publicación: Reino Unido