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Establishment and function of chromatin organization at replication origins

Author

Listed:
  • Erika Chacin

    (Faculty of Medicine, Ludwig-Maximilians-Universität in Munich)

  • Karl-Uwe Reusswig

    (Max Planck Institute of Biochemistry, DNA Replication and Genome Integrity
    Dana-Farber Cancer Institute)

  • Jessica Furtmeier

    (Faculty of Medicine, Ludwig-Maximilians-Universität in Munich)

  • Priyanka Bansal

    (Faculty of Medicine, Ludwig-Maximilians-Universität in Munich)

  • Leonhard A. Karl

    (Max Planck Institute of Biochemistry, DNA Replication and Genome Integrity)

  • Boris Pfander

    (Max Planck Institute of Biochemistry, DNA Replication and Genome Integrity
    Institute of Aerospace Medicine, German Aerospace Center (DLR)
    University of Cologne, Medical Faculty)

  • Tobias Straub

    (Faculty of Medicine, Ludwig-Maximilians-Universität in Munich)

  • Philipp Korber

    (Faculty of Medicine, Ludwig-Maximilians-Universität in Munich)

  • Christoph F. Kurat

    (Faculty of Medicine, Ludwig-Maximilians-Universität in Munich)

Abstract

The origin recognition complex (ORC) is essential for initiation of eukaryotic chromosome replication as it loads the replicative helicase—the minichromosome maintenance (MCM) complex—at replication origins1. Replication origins display a stereotypic nucleosome organization with nucleosome depletion at ORC-binding sites and flanking arrays of regularly spaced nucleosomes2–4. However, how this nucleosome organization is established and whether this organization is required for replication remain unknown. Here, using genome-scale biochemical reconstitution with approximately 300 replication origins, we screened 17 purified chromatin factors from budding yeast and found that the ORC established nucleosome depletion over replication origins and flanking nucleosome arrays by orchestrating the chromatin remodellers INO80, ISW1a, ISW2 and Chd1. The functional importance of the nucleosome-organizing activity of the ORC was demonstrated by orc1 mutations that maintained classical MCM-loader activity but abrogated the array-generation activity of ORC. These mutations impaired replication through chromatin in vitro and were lethal in vivo. Our results establish that ORC, in addition to its canonical role as the MCM loader, has a second crucial function as a master regulator of nucleosome organization at the replication origin, a crucial prerequisite for efficient chromosome replication.

Suggested Citation

  • Erika Chacin & Karl-Uwe Reusswig & Jessica Furtmeier & Priyanka Bansal & Leonhard A. Karl & Boris Pfander & Tobias Straub & Philipp Korber & Christoph F. Kurat, 2023. "Establishment and function of chromatin organization at replication origins," Nature, Nature, vol. 616(7958), pages 836-842, April.
    • Handle: RePEc:nat:nature:v:616:y:2023:i:7958:d:10.1038_s41586-023-05926-8
    DOI: 10.1038/s41586-023-05926-8
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    Cited by:

    1. 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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