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Linking DNA repair and cell cycle progression through serine ADP-ribosylation of histones

Author

Listed:
  • Julien Brustel

    (University of Oxford)

  • Tetsuya Muramoto

    (Toho University)

  • Kazuki Fumimoto

    (Toho University)

  • Jessica Ellins

    (University of Oxford)

  • Catherine J. Pears

    (University of Oxford)

  • Nicholas D. Lakin

    (University of Oxford)

Abstract

Although serine ADP-ribosylation (Ser-ADPr) by Poly(ADP-ribose)-polymerases is a cornerstone of the DNA damage response, how this regulates DNA repair and genome stability is unknown. Here, we exploit the ability to manipulate histone genes in Dictyostelium to identify that ADPr of the histone variant H3b at S10 and S28 maintains genome stability by integrating double strand break (DSB) repair with mitotic entry. Given the critical requirement for mitotic H3S10/28 phosphorylation, we develop separation of function mutations that maintain S10 phosphorylation whilst disrupting ADPr. Mechanistically, this reveals a requirement for H3bS10/28 ADPr in non-homologous end-joining by recruiting Ku to DSBs. Moreover, this also identifies H3bS10/S28 ADPr is critical to prevent premature mitotic entry with unresolved DNA damage, thus maintaining genome stability. Together, these data demonstrate how serine ADPr of histones coordinates DNA repair with cell cycle progression to maintain genome stability.

Suggested Citation

  • Julien Brustel & Tetsuya Muramoto & Kazuki Fumimoto & Jessica Ellins & Catherine J. Pears & Nicholas D. Lakin, 2022. "Linking DNA repair and cell cycle progression through serine ADP-ribosylation of histones," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27867-4
    DOI: 10.1038/s41467-021-27867-4
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    Cited by:

    1. Megha Jhanji & Chintada Nageswara Rao & Jacob C. Massey & Marion C. Hope & Xueyan Zhou & C. Dirk Keene & Tao Ma & Michael D. Wyatt & Jason A. Stewart & Mathew Sajish, 2022. "Cis- and trans-resveratrol have opposite effects on histone serine-ADP-ribosylation and tyrosine induced neurodegeneration," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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