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Spatio-temporal control of DNA replication by the pneumococcal cell cycle regulator CcrZ

View ORCID ProfileClement Gallay, Stefano Sanselicio, Mary E. Anderson, Young Min Soh, View ORCID ProfileXue Liu, View ORCID ProfileGro A. Stamsås, View ORCID ProfileSimone Pelliciari, View ORCID ProfileRenske van Raaphorst, View ORCID ProfileMorten Kjos, View ORCID ProfileHeath Murray, View ORCID ProfileStephan Gruber, View ORCID ProfileAlan D. Grossman, View ORCID ProfileJan-Willem Veening
doi: https://doi.org/10.1101/775536
Clement Gallay
1Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Biophore Building, CH-1015 Lausanne, Switzerland
2Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen, Nijenborgh 7, 9747 AG Groningen, the Netherlands
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Stefano Sanselicio
1Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Biophore Building, CH-1015 Lausanne, Switzerland
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Mary E. Anderson
3Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
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Young Min Soh
1Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Biophore Building, CH-1015 Lausanne, Switzerland
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Xue Liu
1Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Biophore Building, CH-1015 Lausanne, Switzerland
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Gro A. Stamsås
4Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway
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Simone Pelliciari
5Centre for Bacterial Cell Biology, Biosciences Institute, Newcastle University, Newcastle Upon Tyne NE2 4AX, UK
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Renske van Raaphorst
1Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Biophore Building, CH-1015 Lausanne, Switzerland
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Morten Kjos
4Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway
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Heath Murray
5Centre for Bacterial Cell Biology, Biosciences Institute, Newcastle University, Newcastle Upon Tyne NE2 4AX, UK
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Stephan Gruber
1Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Biophore Building, CH-1015 Lausanne, Switzerland
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Alan D. Grossman
3Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
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Jan-Willem Veening
1Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Biophore Building, CH-1015 Lausanne, Switzerland
2Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen, Nijenborgh 7, 9747 AG Groningen, the Netherlands
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  • For correspondence: Jan-Willem.Veening@unil.ch
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Summary

Most bacteria replicate and segregate their DNA concomitantly while growing, before cell division takes place. How bacteria synchronize these different cell cycle events to ensure faithful chromosome inheritance is poorly understood. Here, we identified a conserved and essential protein in pneumococci and related Firmicutes named CcrZ (for Cell Cycle Regulator protein interacting with FtsZ) that couples cell division with DNA replication by controlling the activity of the master initiator of DNA replication, DnaA. The absence of CcrZ causes mis-timed and reduced initiation of DNA replication, which subsequently results in aberrant cell division. We show that CcrZ from Streptococcus pneumoniae directly interacts with the cytoskeleton protein FtsZ to place it in the middle of the newborn cell where the DnaA-bound origin is positioned. Together, this work uncovers a new mechanism for the control of the bacterial cell cycle in which CcrZ controls DnaA activity to ensure that the chromosome is replicated at the right time during the cell cycle.

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Posted September 19, 2019.
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Spatio-temporal control of DNA replication by the pneumococcal cell cycle regulator CcrZ
Clement Gallay, Stefano Sanselicio, Mary E. Anderson, Young Min Soh, Xue Liu, Gro A. Stamsås, Simone Pelliciari, Renske van Raaphorst, Morten Kjos, Heath Murray, Stephan Gruber, Alan D. Grossman, Jan-Willem Veening
bioRxiv 775536; doi: https://doi.org/10.1101/775536
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Spatio-temporal control of DNA replication by the pneumococcal cell cycle regulator CcrZ
Clement Gallay, Stefano Sanselicio, Mary E. Anderson, Young Min Soh, Xue Liu, Gro A. Stamsås, Simone Pelliciari, Renske van Raaphorst, Morten Kjos, Heath Murray, Stephan Gruber, Alan D. Grossman, Jan-Willem Veening
bioRxiv 775536; doi: https://doi.org/10.1101/775536

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