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Nucleosome-directed replication origin licensing independent of a consensus DNA sequence

Author

Listed:
  • Sai Li

    (The Rockefeller University)

  • Michael R. Wasserman

    (The Rockefeller University
    Syros Pharmaceuticals)

  • Olga Yurieva

    (The Rockefeller University
    The Rockefeller University)

  • Lu Bai

    (The Pennsylvania State University
    The Pennsylvania State University
    The Pennsylvania State University)

  • Michael E. O’Donnell

    (The Rockefeller University
    The Rockefeller University)

  • Shixin Liu

    (The Rockefeller University)

Abstract

The numerous enzymes and cofactors involved in eukaryotic DNA replication are conserved from yeast to human, and the budding yeast Saccharomyces cerevisiae (S.c.) has been a useful model organism for these studies. However, there is a gap in our knowledge of why replication origins in higher eukaryotes do not use a consensus DNA sequence as found in S.c. Using in vitro reconstitution and single-molecule visualization, we show here that S.c. origin recognition complex (ORC) stably binds nucleosomes and that ORC-nucleosome complexes have the intrinsic ability to load the replicative helicase MCM double hexamers onto adjacent nucleosome-free DNA regardless of sequence. Furthermore, we find that Xenopus laevis nucleosomes can substitute for yeast ones in engaging with ORC. Combined with re-analyses of genome-wide ORC binding data, our results lead us to propose that the yeast origin recognition machinery contains the cryptic capacity to bind nucleosomes near a nucleosome-free region and license origins, and that this nucleosome-directed origin licensing paradigm generalizes to all eukaryotes.

Suggested Citation

  • Sai Li & Michael R. Wasserman & Olga Yurieva & Lu Bai & Michael E. O’Donnell & Shixin Liu, 2022. "Nucleosome-directed replication origin licensing independent of a consensus DNA sequence," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32657-7
    DOI: 10.1038/s41467-022-32657-7
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    References listed on IDEAS

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    Cited by:

    1. Jérémy Poulet-Benedetti & Caroline Tonnerre-Doncarli & Anne-Laure Valton & Marc Laurent & Marie Gérard & Natalja Barinova & Nikolaos Parisis & Florian Massip & Franck Picard & Marie-Noëlle Prioleau, 2023. "Dimeric G-quadruplex motifs-induced NFRs determine strong replication origins in vertebrates," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Humberto Sánchez & Zhaowei Liu & Edo Veen & Theo Laar & John F. X. Diffley & Nynke H. Dekker, 2023. "A chromatinized origin reduces the mobility of ORC and MCM through interactions and spatial constraint," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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