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Histone H4K20 methylation mediated chromatin compaction threshold ensures genome integrity by limiting DNA replication licensing

Author

Listed:
  • Muhammad Shoaib

    (University of Copenhagen)

  • David Walter

    (University of Copenhagen)

  • Peter J. Gillespie

    (University of Dundee)

  • Fanny Izard

    (Institut Régional du Cancer (ICM))

  • Birthe Fahrenkrog

    (Universite Libré de Bruxelles)

  • David Lleres

    (University of Montpellier, CNRS)

  • Mads Lerdrup

    (University of Copenhagen)

  • Jens Vilstrup Johansen

    (University of Copenhagen)

  • Klaus Hansen

    (University of Copenhagen)

  • Eric Julien

    (Institut Régional du Cancer (ICM)
    Centre National de la Recherche Scientifique (CNRS))

  • J. Julian Blow

    (University of Dundee)

  • Claus S. Sørensen

    (University of Copenhagen)

Abstract

The decompaction and re-establishment of chromatin organization immediately after mitosis is essential for genome regulation. Mechanisms underlying chromatin structure control in daughter cells are not fully understood. Here we show that a chromatin compaction threshold in cells exiting mitosis ensures genome integrity by limiting replication licensing in G1 phase. Upon mitotic exit, chromatin relaxation is controlled by SET8-dependent methylation of histone H4 on lysine 20. In the absence of either SET8 or H4K20 residue, substantial genome-wide chromatin decompaction occurs allowing excessive loading of the origin recognition complex (ORC) in the daughter cells. ORC overloading stimulates aberrant recruitment of the MCM2-7 complex that promotes single-stranded DNA formation and DNA damage. Restoring chromatin compaction restrains excess replication licensing and loss of genome integrity. Our findings identify a cell cycle-specific mechanism whereby fine-tuned chromatin relaxation suppresses excessive detrimental replication licensing and maintains genome integrity at the cellular transition from mitosis to G1 phase.

Suggested Citation

  • Muhammad Shoaib & David Walter & Peter J. Gillespie & Fanny Izard & Birthe Fahrenkrog & David Lleres & Mads Lerdrup & Jens Vilstrup Johansen & Klaus Hansen & Eric Julien & J. Julian Blow & Claus S. Sø, 2018. "Histone H4K20 methylation mediated chromatin compaction threshold ensures genome integrity by limiting DNA replication licensing," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06066-8
    DOI: 10.1038/s41467-018-06066-8
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    Cited by:

    1. Aina Maria Mas & Enrique Goñi & Igor Ruiz de los Mozos & Aida Arcas & Luisa Statello & Jovanna González & Lorea Blázquez & Wei Ting Chelsea Lee & Dipika Gupta & Álvaro Sejas & Shoko Hoshina & Alexandr, 2023. "ORC1 binds to cis-transcribed RNAs for efficient activation of replication origins," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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