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Structure of the origin recognition complex bound to DNA replication origin

Author

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  • Ningning Li

    (Peking-Tsinghua Center for Life Sciences, School of Life Sciences, Peking University)

  • Wai Hei Lam

    (The Hong Kong University of Science and Technology)

  • Yuanliang Zhai

    (The Hong Kong University of Science and Technology
    The Hong Kong University of Science and Technology
    School of Biological Sciences, The University of Hong Kong)

  • Jiaxuan Cheng

    (Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University)

  • Erchao Cheng

    (Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University)

  • Yongqian Zhao

    (The Hong Kong University of Science and Technology
    The Hong Kong University of Science and Technology)

  • Ning Gao

    (Peking-Tsinghua Center for Life Sciences, School of Life Sciences, Peking University)

  • Bik-Kwoon Tye

    (The Hong Kong University of Science and Technology
    Cornell University)

Abstract

The six-subunit origin recognition complex (ORC) binds to DNA to mark the site for the initiation of replication in eukaryotes. Here we report a 3 Å cryo-electron microscopy structure of the Saccharomyces cerevisiae ORC bound to a 72-base-pair origin DNA sequence that contains the ARS consensus sequence (ACS) and the B1 element. The ORC encircles DNA through extensive interactions with both phosphate backbone and bases, and bends DNA at the ACS and B1 sites. Specific recognition of thymine residues in the ACS is carried out by a conserved basic amino acid motif of Orc1 in the minor groove, and by a species-specific helical insertion motif of Orc4 in the major groove. Moreover, similar insertions into major and minor grooves are also embedded in the B1 site by basic patch motifs from Orc2 and Orc5, respectively, to contact bases and to bend DNA. This work pinpoints a conserved role of ORC in modulating DNA structure to facilitate origin selection and helicase loading in eukaryotes.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:nature:v:559:y:2018:i:7713:d:10.1038_s41586-018-0293-x
    DOI: 10.1038/s41586-018-0293-x
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    Cited by:

    1. Jan Marten Schmidt & Ran Yang & Ashish Kumar & Olivia Hunker & Jan Seebacher & Franziska Bleichert, 2022. "A mechanism of origin licensing control through autoinhibition of S. cerevisiae ORC·DNA·Cdc6," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. 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.
    3. Yue Wu & Qiongdan Zhang & Yuhan Lin & Wai Hei Lam & Yuanliang Zhai, 2024. "Replication licensing regulated by a short linear motif within an intrinsically disordered region of origin recognition complex," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    4. 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.
    5. 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.

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