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Structure of the polymerase ε holoenzyme and atomic model of the leading strand replisome

Author

Listed:
  • Zuanning Yuan

    (Van Andel Institute)

  • Roxana Georgescu

    (Howard Hughes Medical Institute
    The Rockefeller University)

  • Grant D. Schauer

    (Howard Hughes Medical Institute
    The Rockefeller University
    Colorado State University)

  • Michael E. O’Donnell

    (Howard Hughes Medical Institute
    The Rockefeller University)

  • Huilin Li

    (Van Andel Institute)

Abstract

The eukaryotic leading strand DNA polymerase (Pol) ε contains 4 subunits, Pol2, Dpb2, Dpb3 and Dpb4. Pol2 is a fusion of two B-family Pols; the N-terminal Pol module is catalytic and the C-terminal Pol module is non-catalytic. Despite extensive efforts, there is no atomic structure for Pol ε holoenzyme, critical to understanding how DNA synthesis is coordinated with unwinding and the DNA path through the CMG helicase-Pol ε-PCNA clamp. We show here a 3.5-Å cryo-EM structure of yeast Pol ε revealing that the Dpb3–Dpb4 subunits bridge the two DNA Pol modules of Pol2, holding them rigid. This information enabled an atomic model of the leading strand replisome. Interestingly, the model suggests that an OB fold in Dbp2 directs leading ssDNA from CMG to the Pol ε active site. These results complete the DNA path from entry of parental DNA into CMG to exit of daughter DNA from PCNA.

Suggested Citation

  • Zuanning Yuan & Roxana Georgescu & Grant D. Schauer & Michael E. O’Donnell & Huilin Li, 2020. "Structure of the polymerase ε holoenzyme and atomic model of the leading strand replisome," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16910-5
    DOI: 10.1038/s41467-020-16910-5
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    Cited by:

    1. Zhichun Xu & Jianrong Feng & Daqi Yu & Yunjing Huo & Xiaohui Ma & Wai Hei Lam & Zheng Liu & Xiang David Li & Toyotaka Ishibashi & Shangyu Dang & Yuanliang Zhai, 2023. "Synergism between CMG helicase and leading strand DNA polymerase at replication fork," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Sameera Vipat & Dipika Gupta & Sagun Jonchhe & Hele Anderspuk & Eli Rothenberg & Tatiana N. Moiseeva, 2022. "The non-catalytic role of DNA polymerase epsilon in replication initiation in human cells," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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