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A chromatinized origin reduces the mobility of ORC and MCM through interactions and spatial constraint

Author

Listed:
  • Humberto Sánchez

    (Delft University of Technology)

  • Zhaowei Liu

    (Delft University of Technology)

  • Edo Veen

    (Delft University of Technology)

  • Theo Laar

    (Delft University of Technology)

  • John F. X. Diffley

    (Francis Crick Institute)

  • Nynke H. Dekker

    (Delft University of Technology)

Abstract

Chromatin replication involves the assembly and activity of the replisome within the nucleosomal landscape. At the core of the replisome is the Mcm2-7 complex (MCM), which is loaded onto DNA after binding to the Origin Recognition Complex (ORC). In yeast, ORC is a dynamic protein that diffuses rapidly along DNA, unless halted by origin recognition sequences. However, less is known about the dynamics of ORC proteins in the presence of nucleosomes and attendant consequences for MCM loading. To address this, we harnessed an in vitro single-molecule approach to interrogate a chromatinized origin of replication. We find that ORC binds the origin of replication with similar efficiency independently of whether the origin is chromatinized, despite ORC mobility being reduced by the presence of nucleosomes. Recruitment of MCM also proceeds efficiently on a chromatinized origin, but subsequent movement of MCM away from the origin is severely constrained. These findings suggest that chromatinized origins in yeast are essential for the local retention of MCM, which may facilitate subsequent assembly of the replisome.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42524-8
    DOI: 10.1038/s41467-023-42524-8
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    References listed on IDEAS

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    1. 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.
    2. 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.
    3. 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.
    4. 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.
    5. Jordi Frigola & Dirk Remus & Amina Mehanna & John F. X. Diffley, 2013. "ATPase-dependent quality control of DNA replication origin licensing," Nature, Nature, vol. 495(7441), pages 339-343, March.
    6. Pablo De Ioannes & Victor A. Leon & Zheng Kuang & Miao Wang & Jef D. Boeke & Andreas Hochwagen & Karim-Jean Armache, 2019. "Structure and function of the Orc1 BAH-nucleosome complex," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    7. Maxim Y. Sheinin & Ming Li & Mohammad Soltani & Karolin Luger & Michelle D. Wang, 2013. "Torque modulates nucleosome stability and facilitates H2A/H2B dimer loss," Nature Communications, Nature, vol. 4(1), pages 1-8, December.
    8. Max E. Douglas & Ferdos Abid Ali & Alessandro Costa & John F. X. Diffley, 2018. "The mechanism of eukaryotic CMG helicase activation," Nature, Nature, vol. 555(7695), pages 265-268, March.
    9. 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.
    10. 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.
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