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Nuclear organisation and replication timing are coupled through RIF1–PP1 interaction

Author

Listed:
  • Stefano Gnan

    (European Molecular Biology Laboratory (EMBL Rome)
    School of Biological Sciences University of Edinburgh
    Dynamics of Genetic Information)

  • Ilya M. Flyamer

    (University of Edinburgh)

  • Kyle N. Klein

    (Florida State University)

  • Eleonora Castelli

    (School of Biological Sciences University of Edinburgh
    Friedrich Miescher Institute for Biomedical Research)

  • Alexander Rapp

    (Technical University of Darmstadt)

  • Andreas Maiser

    (LMU Munich)

  • Naiming Chen

    (School of Biological Sciences University of Edinburgh)

  • Patrick Weber

    (Technical University of Darmstadt)

  • Elin Enervald

    (European Molecular Biology Laboratory (EMBL Rome)
    School of Biological Sciences University of Edinburgh
    The Wenner-Gren Institute, Stockholm University)

  • M. Cristina Cardoso

    (Technical University of Darmstadt)

  • Wendy A. Bickmore

    (University of Edinburgh)

  • David M. Gilbert

    (Florida State University)

  • Sara C. B. Buonomo

    (European Molecular Biology Laboratory (EMBL Rome)
    School of Biological Sciences University of Edinburgh)

Abstract

Three-dimensional genome organisation and replication timing are known to be correlated, however, it remains unknown whether nuclear architecture overall plays an instructive role in the replication-timing programme and, if so, how. Here we demonstrate that RIF1 is a molecular hub that co-regulates both processes. Both nuclear organisation and replication timing depend upon the interaction between RIF1 and PP1. However, whereas nuclear architecture requires the full complement of RIF1 and its interaction with PP1, replication timing is not sensitive to RIF1 dosage. The role of RIF1 in replication timing also extends beyond its interaction with PP1. Availing of this separation-of-function approach, we have therefore identified in RIF1 dual function the molecular bases of the co-dependency of the replication-timing programme and nuclear architecture.

Suggested Citation

  • Stefano Gnan & Ilya M. Flyamer & Kyle N. Klein & Eleonora Castelli & Alexander Rapp & Andreas Maiser & Naiming Chen & Patrick Weber & Elin Enervald & M. Cristina Cardoso & Wendy A. Bickmore & David M., 2021. "Nuclear organisation and replication timing are coupled through RIF1–PP1 interaction," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22899-2
    DOI: 10.1038/s41467-021-22899-2
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    Cited by:

    1. Jamie L. Endicott & Paula A. Nolte & Hui Shen & Peter W. Laird, 2022. "Cell division drives DNA methylation loss in late-replicating domains in primary human cells," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Stefano Gnan & Joseph M. Josephides & Xia Wu & Manuela Spagnuolo & Dalila Saulebekova & Mylène Bohec & Marie Dumont & Laura G. Baudrin & Daniele Fachinetti & Sylvain Baulande & Chun-Long Chen, 2022. "Kronos scRT: a uniform framework for single-cell replication timing analysis," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Daniel Malzl & Mihaela Peycheva & Ali Rahjouei & Stefano Gnan & Kyle N. Klein & Mariia Nazarova & Ursula E. Schoeberl & David M. Gilbert & Sara C. B. Buonomo & Michela Virgilio & Tobias Neumann & Rush, 2023. "RIF1 regulates early replication timing in murine B cells," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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