Ctf4 organizes sister replisomes and Pol α into a replication factory
- Van Andel Institute, United States
- Howard Hughes Medical Institute, The Rockefeller University, United States
- 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.
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3D cryo-EM map of Ctf43-CMG1Electron Microscopy Data Bank, EMD-20471.
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3D cryo-EM maps of Ctf43-CMG2Electron Microscopy Data Bank, EMD-20472.
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3D cryo-EM maps of Ctf43-CMG3Electron Microscopy Data Bank, EMD-20473.
Article and author information
Author details
Michael E O'Donnell
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.
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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Ctf4 organizes sister replisomes and Pol α into a replication factory
eLife 8:e47405.
https://doi.org/10.7554/eLife.47405
Further reading
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In the bacterium M. smegmatis, an enzyme called MftG allows the cofactor mycofactocin to transfer electrons released during ethanol metabolism to the electron transport chain.
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