Ctf4 organizes sister replisomes and Pol α into a replication factory

  1. Zuanning Yuan
  2. Roxana Georgescu
  3. Ruda de Luna Almeida Santos
  4. Daniel Zhang
  5. Lin Bai
  6. Nina Y Yao
  7. Gongpu Zhao
  8. Michael E O'Donnell  Is a corresponding author
  9. Huilin Li  Is a corresponding author
  1. Van Andel Institute, United States
  2. Howard Hughes Medical Institute, The Rockefeller University, United States
  3. The Rockefeller University, United States

Abstract

The current view is that eukaryotic replisomes are independent. Here we show that Ctf4 tightly dimerizes CMG helicase, with an extensive interface involving Psf2, Cdc45, and Sld5. Interestingly, Ctf4 binds only one Pol α-primase. Thus, Ctf4 may have evolved as a trimer to organize two helicases and one Pol α-primase into a replication factory. In the 2CMG-Ctf43-1Pol α-primase factory model, the two CMGs nearly face each other, placing the two lagging strands toward the center and two leading strands out the sides. The single Pol α-primase is centrally located and may prime both sister replisomes. The Ctf4-coupled-sister replisome model is consistent with cellular microscopy studies revealing two sister forks of an origin remain attached and are pushed forward from a protein platform. The replication factory model may facilitate parental nucleosome transfer during replication.

Data availability

The 3D cryo-EM maps of Ctf43-CMG1, Ctf43-CMG2, and Ctf43-CMG3 at 3.8-Å, 5.8-Å and 7.0-Å resolution have been deposited in the Electron Microscopy Data Bank under accession codes EMD-20471, EMD-20472 and EMD-20473, respectively. The corresponding atomic models have been deposited in the Protein Data Bank under accession codes PDB 6PTJ, PDB 6PTN, PDB 6PTO, respectively.

The following data sets were generated

Article and author information

Author details

  1. Zuanning Yuan

    Structural Biology Program, Van Andel Institute, Grand Rapids, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Roxana Georgescu

    Howard Hughes Medical Institute, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1882-2358
  3. Ruda de Luna Almeida Santos

    Structural Biology Program, Van Andel Institute, Grand Rapids, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Daniel Zhang

    DNA Replication Laboratory, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Lin Bai

    Structural Biology Program, Van Andel Institute, Grand Rapids, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Nina Y Yao

    DNA Replication Laboratory, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Gongpu Zhao

    David Van Andel Advanced Cryo-EM Suite, Van Andel Institute, Grand Rapids, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Michael E O'Donnell

    Howard Hughes Medical Institute, The Rockefeller University, New York, United States
    For correspondence
    odonnel@rockefeller.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9002-4214
  9. Huilin Li

    Structural Biology Program, Van Andel Institute, Grand Rapids, United States
    For correspondence
    Huilin.Li@vai.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8085-8928

Funding

National Institutes of Health (GM115809)

  • Michael E O'Donnell

National Institutes of Health (GM131754)

  • Huilin Li

Howard Hughes Medical Institute

  • Michael E O'Donnell

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

Reviewing Editor

  1. James M Berger, Johns Hopkins University School of Medicine, United States

Version history

  1. Received: April 4, 2019
  2. Accepted: October 4, 2019
  3. Accepted Manuscript published: October 7, 2019 (version 1)
  4. Version of Record published: October 18, 2019 (version 2)

Copyright

© 2019, Yuan 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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  1. Zuanning Yuan
  2. Roxana Georgescu
  3. Ruda de Luna Almeida Santos
  4. Daniel Zhang
  5. Lin Bai
  6. Nina Y Yao
  7. Gongpu Zhao
  8. Michael E O'Donnell
  9. Huilin Li
(2019)
Ctf4 organizes sister replisomes and Pol α into a replication factory
eLife 8:e47405.
https://doi.org/10.7554/eLife.47405

Share this article

https://doi.org/10.7554/eLife.47405

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