Imperial College London
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DrRachelEdgar

Faculty of Medicine, Department of Infectious Disease

Sir Henry Dale Fellow
 
 
 
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Contact

 

rachel.edgar Website

 
 
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Location

 

11Medical SchoolSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Putker:2021:10.15252/embj.2020106745,
author = {Putker, M and Wong, DCS and Seinkmane, E and Rzechorzek, NM and Zeng, A and Hoyle, NP and Chesham, JE and Edwards, MD and Feeney, KA and Fischer, R and Peschel, N and Chen, K-F and Vanden, Oever M and Edgar, RS and Selby, CP and Sancar, A and O'Neill, JS},
doi = {10.15252/embj.2020106745},
journal = {The EMBO Journal},
pages = {1--15},
title = {CRYPTOCHROMES confer robustness, not rhythmicity, to circadian timekeeping},
url = {http://dx.doi.org/10.15252/embj.2020106745},
volume = {40},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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 CRYdeficient (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. CRYless oscillations are variable in their expression and have shorter periods than wildtype 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 CRYmediated 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 posttranslational.
AU  - Putker,M
AU  - Wong,DCS
AU  - Seinkmane,E
AU  - Rzechorzek,NM
AU  - Zeng,A
AU  - Hoyle,NP
AU  - Chesham,JE
AU  - Edwards,MD
AU  - Feeney,KA
AU  - Fischer,R
AU  - Peschel,N
AU  - Chen,K-F
AU  - Vanden,Oever M
AU  - Edgar,RS
AU  - Selby,CP
AU  - Sancar,A
AU  - O'Neill,JS
DO  - 10.15252/embj.2020106745
EP  - 15
PY  - 2021///
SN  - 0261-4189
SP  - 1
TI  - CRYPTOCHROMES confer robustness, not rhythmicity, to circadian timekeeping
T2  - The EMBO Journal
UR  - http://dx.doi.org/10.15252/embj.2020106745
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000611039100001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.embopress.org/doi/full/10.15252/embj.2020106745
UR  - http://hdl.handle.net/10044/1/87225
VL  - 40
ER  -
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