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Molecular choreography of primer synthesis by the eukaryotic Pol α-primase

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  • Zuanning Yuan

    (Van Andel Institute)

  • Roxana Georgescu

    (Rockefeller University)

  • Huilin Li

    (Van Andel Institute)

  • Michael E. O’Donnell

    (Rockefeller University)

Abstract

The eukaryotic polymerase α (Pol α) synthesizes an RNA-DNA hybrid primer of 20–30 nucleotides. Pol α is composed of Pol1, Pol12, Primase 1 (Pri1), and Pri2. Pol1 and Pri1 contain the DNA polymerase and RNA primase activities, respectively. It has been unclear how Pol α hands over an RNA primer from Pri1 to Pol1 for DNA primer extension, and how the primer length is defined. Here we report the cryo-EM analysis of yeast Pol α in the apo, primer initiation, primer elongation, RNA primer hand-off from Pri1 to Pol1, and DNA extension states, revealing a series of very large movements. We reveal a critical point at which Pol1-core moves to take over the 3’-end of the RNA from Pri1. DNA extension is limited by a spiral motion of Pol1-core. Since both Pri1 and Pol1-core are flexibly attached to a stable platform, primer growth produces stress that limits the primer length.

Suggested Citation

  • Zuanning Yuan & Roxana Georgescu & Huilin Li & Michael E. O’Donnell, 2023. "Molecular choreography of primer synthesis by the eukaryotic Pol α-primase," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39441-1
    DOI: 10.1038/s41467-023-39441-1
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    References listed on IDEAS

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    1. Qixiang He & Xiuhua Lin & Bianca L. Chavez & Sourav Agrawal & Benjamin L. Lusk & Ci Ji Lim, 2022. "Structures of the human CST-Polα–primase complex bound to telomere templates," Nature, Nature, vol. 608(7924), pages 826-832, August.
    2. Yao He & He Song & Henry Chan & Baocheng Liu & Yaqiang Wang & Lukas Sušac & Z. Hong Zhou & Juli Feigon, 2022. "Structure of Tetrahymena telomerase-bound CST with polymerase α-primase," Nature, Nature, vol. 608(7924), pages 813-818, August.
    3. Sandro Holzer & Jiangyu Yan & Mairi L. Kilkenny & Stephen D. Bell & Luca Pellegrini, 2017. "Primer synthesis by a eukaryotic-like archaeal primase is independent of its Fe-S cluster," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    4. Marta A. Garbacz & Scott A. Lujan & Adam B. Burkholder & Phillip B. Cox & Qiuqin Wu & Zhi-Xiong Zhou & James E. Haber & Thomas A. Kunkel, 2018. "Evidence that DNA polymerase δ contributes to initiating leading strand DNA replication in Saccharomyces cerevisiae," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
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