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FBL17 targets CDT1a for degradation in early S-phase to prevent Arabidopsis genome instability

Bénédicte Desvoyes, View ORCID ProfileSandra Noir, Kinda Masoud, María Isabel López, Pascal Genschik, View ORCID ProfileCrisanto Gutierrez
doi: https://doi.org/10.1101/774109
Bénédicte Desvoyes
1Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Nicolás Cabrera 1, Cantoblanco, 28049 Madrid, Spain
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  • For correspondence: cgutierrez@cbm.csic.es bdesvoyes@cbm.csic.es
Sandra Noir
2Institut de Biologie Moléculaire des Plantes, CNRS-UPR2357, Université de Strasbourg, 12 rue Général Zimmer, 67084 Strasbourg cedex, France
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Kinda Masoud
2Institut de Biologie Moléculaire des Plantes, CNRS-UPR2357, Université de Strasbourg, 12 rue Général Zimmer, 67084 Strasbourg cedex, France
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María Isabel López
1Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Nicolás Cabrera 1, Cantoblanco, 28049 Madrid, Spain
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Pascal Genschik
2Institut de Biologie Moléculaire des Plantes, CNRS-UPR2357, Université de Strasbourg, 12 rue Général Zimmer, 67084 Strasbourg cedex, France
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Crisanto Gutierrez
1Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Nicolás Cabrera 1, Cantoblanco, 28049 Madrid, Spain
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  • ORCID record for Crisanto Gutierrez
  • For correspondence: cgutierrez@cbm.csic.es bdesvoyes@cbm.csic.es
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Abstract

Maintenance of genome integrity depends on controlling the availability of DNA replication initiation proteins, e.g., CDT1, a component of the pre-replication complexes that regulates chromatin licensing for replication. To understand the evolutionary history of CDT1 regulation, we have identified the mechanisms involved in CDT1 dynamics. During cell cycle, CDT1a starts to be loaded early after mitotic exit and maintains high levels until the G1/S transition. Soon after the S-phase onset, CDT1a is rapidly degraded in a proteasome-dependent manner. Plant cells use a specific SCF-mediated pathway that relies on the FBL17 F-box protein for CDT1a degradation, which is independent of CUL4a-containing complexes. A similar oscillatory pattern occurs in endoreplicating cells, where CDT1a is loaded just after finishing the S-phase. CDT1a is necessary to maintain genome stability, an ancient strategy although unique proteins and mechanisms have evolved in different eukaryotic lineages to ensure its degradation during S-phase.

Impact statement The DNA replication protein CDT1a is crucial for genome integrity and is targeted for proteasome degradation just after S-phase initiation by FBL17 in proliferating and endoreplicating cells of Arabidopsis

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted September 20, 2019.
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FBL17 targets CDT1a for degradation in early S-phase to prevent Arabidopsis genome instability
Bénédicte Desvoyes, Sandra Noir, Kinda Masoud, María Isabel López, Pascal Genschik, Crisanto Gutierrez
bioRxiv 774109; doi: https://doi.org/10.1101/774109
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FBL17 targets CDT1a for degradation in early S-phase to prevent Arabidopsis genome instability
Bénédicte Desvoyes, Sandra Noir, Kinda Masoud, María Isabel López, Pascal Genschik, Crisanto Gutierrez
bioRxiv 774109; doi: https://doi.org/10.1101/774109

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