1. Cell Biology
  2. Computational and Systems Biology
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The nucleus serves as the pacemaker for the cell cycle

  1. Oshri Afanzar
  2. Garrison K Buss
  3. Tim Stearns
  4. James E Ferrell Jr.  Is a corresponding author
  1. Stanford Medicine, United States
  2. Stanford University, United States
Research Article
  • Cited 7
  • Views 3,146
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Cite this article as: eLife 2020;9:e59989 doi: 10.7554/eLife.59989


Mitosis is a dramatic process that affects all parts of the cell. It is driven by an oscillator whose various components are localized in the nucleus, centrosome, and cytoplasm. In principle, the cellular location with the fastest intrinsic rhythm should act as a pacemaker for the process. Here we traced the waves of tubulin polymerization and depolymerization that occur at mitotic entry and exit in Xenopus egg extracts back to their origins. We found that mitosis was commonly initiated at sperm-derived nuclei and their accompanying centrosomes. The cell cycle was ~20% faster at these initiation points than in the slowest regions of the extract. Nuclei produced from phage DNA, which did not possess centrosomes, also acted as trigger wave sources, but purified centrosomes in the absence of nuclei did not. We conclude that the nucleus accelerates mitotic entry and propose that it acts as a pacemaker for cell cycle.

Data availability

All data and code used in the analysis are available from the Stanford Digital Repository (https://purl.stanford.edu/fm814ch0699) for purposes of reproducing or extending the analysis.

The following data sets were generated

Article and author information

Author details

  1. Oshri Afanzar

    Chemical and Systems Biology, Stanford Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Garrison K Buss

    Molecular and Cellular Physiology, Stanford Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Tim Stearns

    Department of Biology, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0671-6582
  4. James E Ferrell Jr.

    Department of Chemical and Systems Biology and Department of Biochemistry, Stanford Medicine, Stanford, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4767-3926


National Institutes of Health (R01 GM110564)

  • James E Ferrell Jr.

National Institutes of Health (R35 GM131792)

  • James E Ferrell Jr.

National Institutes of Health (R35 GM120286)

  • Tim Stearns

National Institutes of Health (GM007276)

  • Garrison K Buss

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.


Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols Stanford University (assurance no. A3213-01, protocol 13307).

Reviewing Editor

  1. Stefano Di Talia, Duke University, United States

Publication history

  1. Received: June 15, 2020
  2. Accepted: December 6, 2020
  3. Accepted Manuscript published: December 7, 2020 (version 1)
  4. Version of Record published: December 22, 2020 (version 2)
  5. Version of Record updated: December 23, 2020 (version 3)


© 2020, Afanzar et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


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