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RIF1 regulates early replication timing in murine B cells

Author

Listed:
  • Daniel Malzl

    (Research Institute of Molecular Pathology (IMP), Vienna Biocenter
    CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

  • Mihaela Peycheva

    (Research Institute of Molecular Pathology (IMP), Vienna Biocenter
    CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

  • Ali Rahjouei

    (Max-Delbruck Center for Molecular Medicine in the Helmholtz Association (MDC))

  • Stefano Gnan

    (University of Edinburgh)

  • Kyle N. Klein

    (San Diego Biomedical Research Institute)

  • Mariia Nazarova

    (Research Institute of Molecular Pathology (IMP), Vienna Biocenter)

  • Ursula E. Schoeberl

    (Research Institute of Molecular Pathology (IMP), Vienna Biocenter)

  • David M. Gilbert

    (San Diego Biomedical Research Institute)

  • Sara C. B. Buonomo

    (University of Edinburgh)

  • Michela Virgilio

    (Max-Delbruck Center for Molecular Medicine in the Helmholtz Association (MDC))

  • Tobias Neumann

    (Research Institute of Molecular Pathology (IMP), Vienna Biocenter
    Quantro Therapeutics, Vienna Biocenter)

  • Rushad Pavri

    (Research Institute of Molecular Pathology (IMP), Vienna Biocenter)

Abstract

The mammalian DNA replication timing (RT) program is crucial for the proper functioning and integrity of the genome. The best-known mechanism for controlling RT is the suppression of late origins of replication in heterochromatin by RIF1. Here, we report that in antigen-activated, hypermutating murine B lymphocytes, RIF1 binds predominantly to early-replicating active chromatin and promotes early replication, but plays a minor role in regulating replication origin activity, gene expression and genome organization in B cells. Furthermore, we find that RIF1 functions in a complementary and non-epistatic manner with minichromosome maintenance (MCM) proteins to establish early RT signatures genome-wide and, specifically, to ensure the early replication of highly transcribed genes. These findings reveal additional layers of regulation within the B cell RT program, driven by the coordinated activity of RIF1 and MCM proteins.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43778-y
    DOI: 10.1038/s41467-023-43778-y
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    1. Eleni Kabrani & Ali Rahjouei & Maria Berruezo-Llacuna & Svenja Ebeling & Tannishtha Saha & Robert Altwasser & Veronica Delgado-Benito & Rushad Pavri & Michela Virgilio, 2025. "RIF1 integrates DNA repair and transcriptional requirements during the establishment of humoral immune responses," Nature Communications, Nature, vol. 16(1), pages 1-17, December.

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