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RIF1 ensures the organization of replication factories upon DNA replicative stress

View ORCID ProfileCyril Ribeyre, Marion Larroque, Christian Larroque, View ORCID ProfileAngelos Constantinou
doi: https://doi.org/10.1101/669234
Cyril Ribeyre
Institut de Génétique Humaine (UMR9002), Centre National de la Recherche Scientifique, Université de Montpellier. 141, Rue de la Cardonille, 34396 Montpellier Cedex 5, France
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  • ORCID record for Cyril Ribeyre
  • For correspondence: cyril.ribeyre@igh.cnrs.fr angelos.constantinou@igh.cnrs.fr
Marion Larroque
Institut du Cancer de Montpellier, Montpellier, France, 208, Avenue des Apothicaires, 34298 Montpellier Cedex 5, France
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Christian Larroque
Institut de Recherche en Cancérologie de Montpellier (U1194), Université de Montpellier, Institut National de la Santé et de la Recherche Médicale, 208, avenue des Apothicaires, 34298 Montpellier Cedex 5, France
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Angelos Constantinou
Institut de Génétique Humaine (UMR9002), Centre National de la Recherche Scientifique, Université de Montpellier. 141, Rue de la Cardonille, 34396 Montpellier Cedex 5, France
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  • ORCID record for Angelos Constantinou
  • For correspondence: cyril.ribeyre@igh.cnrs.fr angelos.constantinou@igh.cnrs.fr
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Abstract

Eukaryotic genomes are duplicated from thousands of replication origins that fire sequentially forming a defined spatiotemporal pattern of replication clusters. The importance of the organization of replisomes into functional clusters, also called replication factories, is still poorly understood. Here we identified the multifunctional protein RIF1 as a structural component of replication factories. RIF1 depletion did not impair the velocity of replication forks, neither in basic conditions nor in presence of a molecule that interferes with replication fork progression but increased the frequency of DNA lesions induced in S phase. Isolation of replication-associated proteins from RIF1-depleted cells revealed a major defect in the clustering of replication factors on nascent DNA, without any noticeable impact on DNA synthesis or replisome stability. We found that the changes in replication patterns commonly observed upon RIF1 depletion are induced by DNA replication stress. The data suggest that RIF1 encases replication factories to ensure the organization of replication clusters against chromatin rearrangements induced by DNA replication stress.

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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-NC-ND 4.0 International license.
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Posted June 12, 2019.
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RIF1 ensures the organization of replication factories upon DNA replicative stress
Cyril Ribeyre, Marion Larroque, Christian Larroque, Angelos Constantinou
bioRxiv 669234; doi: https://doi.org/10.1101/669234
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RIF1 ensures the organization of replication factories upon DNA replicative stress
Cyril Ribeyre, Marion Larroque, Christian Larroque, Angelos Constantinou
bioRxiv 669234; doi: https://doi.org/10.1101/669234

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