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MCM2-7 loading-dependent ORC release ensures genome-wide origin licensing

Author

Listed:
  • L. Maximilian Reuter

    (Imperial College London
    Ackermannweg 4)

  • Sanjay P. Khadayate

    (MRC London Institute of Medical Sciences (LMS))

  • Audrey Mossler

    (Imperial College London)

  • Korbinian Liebl

    (The University of Chicago)

  • Sarah V. Faull

    (Imperial College London)

  • Mohammad M. Karimi

    (MRC London Institute of Medical Sciences (LMS)
    King’s College London)

  • Christian Speck

    (Imperial College London
    MRC London Institute of Medical Sciences (LMS))

Abstract

Origin recognition complex (ORC)-dependent loading of the replicative helicase MCM2-7 onto replication origins in G1-phase forms the basis of replication fork establishment in S-phase. However, how ORC and MCM2-7 facilitate genome-wide DNA licensing is not fully understood. Mapping the molecular footprints of budding yeast ORC and MCM2-7 genome-wide, we discovered that MCM2-7 loading is associated with ORC release from origins and redistribution to non-origin sites. Our bioinformatic analysis revealed that origins are compact units, where a single MCM2-7 double hexamer blocks repetitive loading through steric ORC binding site occlusion. Analyses of A-elements and an improved B2-element consensus motif uncovered that DNA shape, DNA flexibility, and the correct, face-to-face spacing of the two DNA elements are hallmarks of ORC-binding and efficient helicase loading sites. Thus, our work identified fundamental principles for MCM2-7 helicase loading that explain how origin licensing is realised across the genome.

Suggested Citation

  • L. Maximilian Reuter & Sanjay P. Khadayate & Audrey Mossler & Korbinian Liebl & Sarah V. Faull & Mohammad M. Karimi & Christian Speck, 2024. "MCM2-7 loading-dependent ORC release ensures genome-wide origin licensing," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51538-9
    DOI: 10.1038/s41467-024-51538-9
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    References listed on IDEAS

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    1. Joseph T. P. Yeeles & Tom D. Deegan & Agnieszka Janska & Anne Early & John F. X. Diffley, 2015. "Regulated eukaryotic DNA replication origin firing with purified proteins," Nature, Nature, vol. 519(7544), pages 431-435, March.
    2. Jan Marten Schmidt & Franziska Bleichert, 2020. "Structural mechanism for replication origin binding and remodeling by a metazoan origin recognition complex and its co-loader Cdc6," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    3. Ningning Li & Wai Hei Lam & Yuanliang Zhai & Jiaxuan Cheng & Erchao Cheng & Yongqian Zhao & Ning Gao & Bik-Kwoon Tye, 2018. "Structure of the origin recognition complex bound to DNA replication origin," Nature, Nature, vol. 559(7713), pages 217-222, July.
    4. Thomas C. R. Miller & Julia Locke & Julia F. Greiwe & John F. X. Diffley & Alessandro Costa, 2019. "Mechanism of head-to-head MCM double-hexamer formation revealed by cryo-EM," Nature, Nature, vol. 575(7784), pages 704-710, November.
    5. Ferdos Abid Ali & Max E. Douglas & Julia Locke & Valerie E. Pye & Andrea Nans & John F. X. Diffley & Alessandro Costa, 2017. "Cryo-EM structure of a licensed DNA replication origin," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
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