Evidence map›Paper›PMID 34618577›Full record

ArticleScience (New York, N.Y.)2021

Reconstitution of an intact clock reveals mechanisms of circadian timekeeping.

Archana G Chavan, Jeffrey A Swan, Joel Heisler, Cigdem Sancar, Dustin C Ernst, Mingxu Fang, Joseph G Palacios, Rebecca K Spangler, Clive R Bagshaw, Sarvind Tripathi and 4 more

Abstract read
In one paragraph

Article in Science (New York, N.Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

50 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Revitalizing the "biology" in "chronobiology".Npj biological timing and sleep · 2026
    Review
  6. The Phenotypic Landscape of a Circadian Clock.bioRxiv : the preprint server for biology · 2026
    Article
  7. Intrinsic period stability of the cyanobacterial circadian oscillator across in vitro and in vivo conditions.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Mutations in the circadian cycle drive adaptive plasticity in cyanobacteria.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  14. Article
  15. Temporal regulation of metabolic processes in the marine diazotrophbioRxiv : the preprint server for biology · 2025
    Article
  16. Article
  17. Article
  18. Article
  19. Life on Venus?Life (Basel, Switzerland) · 2025
    Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Archana G Chavan *School of Natural Sciences, University of California, Merced, CA 95343, USA.ORCID 0000-0002-5691-8094
Jeffrey A Swan *Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA.ORCID 0000-0002-4487-328X
Joel Heisler *Department of Chemistry and Biochemistry, University of California, Merced, CA 95343, USA.ORCID 0000-0002-2703-3035
Cigdem SancarCenter for Circadian Biology, University of California, San Diego, La Jolla, CA 92093, USA.ORCID 0000-0002-7242-8757
Dustin C ErnstCenter for Circadian Biology, University of California, San Diego, La Jolla, CA 92093, USA.ORCID 0000-0001-8762-960X
Mingxu FangCenter for Circadian Biology, University of California, San Diego, La Jolla, CA 92093, USA.ORCID 0000-0003-1595-8046
Joseph G PalaciosDepartment of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA.
Rebecca K SpanglerDepartment of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA.ORCID 0000-0001-5021-0661
Clive R BagshawDepartment of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA.ORCID 0000-0002-5396-153X
Sarvind TripathiDepartment of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA.ORCID 0000-0002-6959-0577
Priya CrosbyDepartment of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA.ORCID 0000-0002-7532-7708
Susan S GoldenCenter for Circadian Biology, University of California, San Diego, La Jolla, CA 92093, USA.ORCID 0000-0002-4264-7019
Carrie L PartchDepartment of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA.ORCID 0000-0002-4677-2861
Andy LiWangSchool of Natural Sciences, University of California, Merced, CA 95343, USA.ORCID 0000-0003-4741-6946

Funding

UNIVERSITY OF CALIFORNIA, SANTA CRUZ IMSD PROGRAMR25GM058903 · NIGMS · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI JURICA, MELISSA S · 1999 to 2019
$12.2M
Resource for Biocomputing Visualization and InformaticsP41GM103311 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 2012 to 2017
$8.2M
Undergraduate Summer Research Experience: Molecular and cellular mechanisms of circadian timekeeping in a prokaryote modelR35GM118290 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GOLDEN, SUSAN S · 2016 to 2025
$6.7M
ChimeraX -- Next Generation Visualization and Analysis Software for Multiscale ModelingR01GM129325 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 2018 to 2025
$5.2M
Structures and mechanisms of circadian rhythms from cyanobacteria to humansR35GM141849 · NIGMS · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI PARTCH, CARRIE L · 2021 to 2025
$4.6M
The Linchpin that Joins the Circadian Oscillator to Clock OutputR01GM107521 · NIGMS · UNIVERSITY OF CALIFORNIA, MERCED · PI LIWANG, ANDY · 2014 to 2021
$2.8M
Atomic resolution analysis of timekeeping by a protein-based circadian clockR01GM121507 · NIGMS · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI PARTCH, CARRIE L · 2017 to 2020
$1.8M
NIGMS NIH HHS P41 GM103311NIGMS NIH HHS R01 GM107521NIGMS NIH HHS R01 GM121507NIGMS NIH HHS R01 GM129325NIGMS NIH HHS R25 GM058903NIGMS NIH HHS R35 GM118290NIGMS NIH HHS R35 GM141849
6 · The paper itself

Abstract

Circadian clocks control gene expression to provide an internal representation of local time. We report reconstitution of a complete cyanobacterial circadian clock in vitro, including the central oscillator, signal transduction pathways, downstream transcription factor, and promoter DNA. The entire system oscillates autonomously and remains phase coherent for many days with a fluorescence-based readout that enables real-time observation of each component simultaneously without user intervention. We identified the molecular basis for loss of cycling in an arrhythmic mutant and explored fundamental mechanisms of timekeeping in the cyanobacterial clock. We find that SasA, a circadian sensor histidine kinase associated with clock output, engages directly with KaiB on the KaiC hexamer to regulate period and amplitude of the central oscillator. SasA uses structural mimicry to cooperatively recruit the rare, fold-switched conformation of KaiB to the KaiC hexamer to form the nighttime repressive complex and enhance rhythmicity of the oscillator, particularly under limiting concentrations of KaiB. Thus, the expanded in vitro clock reveals previously unknown mechanisms by which the circadian system of cyanobacteria maintains the pace and rhythmicity under variable protein concentrations.

Indexed as

Bacterial ProteinsCircadian RhythmCircadian Rhythm Signaling Peptides and ProteinsGene Expression Regulation, BacterialMolecular MimicryMutationPhosphotransferasesPromoter Regions, GeneticProtein DomainsProtein FoldingProtein KinasesProtein MultimerizationSynechococcusTranscription, GeneticBacterial ProteinsCikA protein, bacteriaCircadian Rhythm Signaling Peptides and ProteinsKaiB protein, cyanobacteriaKaiC protein, cyanobacteriaPhosphotransferasesProtein KinasesSasA protein, Synechococcus

Identifiers

PMID34618577
PMCPMC8686788

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Registered trials

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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.