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DNA translocation mechanism of the MCM complex and implications for replication initiation

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Listed:
  • Martin Meagher

    (St Jude Children’s Research Hospital)

  • Leslie B. Epling

    (St Jude Children’s Research Hospital
    Incyte Research Institute)

  • Eric J. Enemark

    (St Jude Children’s Research Hospital)

Abstract

The DNA translocation activity of the minichromosome maintenance (MCM) complex powers DNA strand separation of the replication forks of eukaryotes and archaea. Here we illustrate an atomic level mechanism for this activity with a crystal structure of an archaeal MCM hexamer bound to single-stranded DNA and nucleotide cofactors. Sequence conservation indicates this rotary mechanism is fully possible for all eukaryotes and archaea. The structure definitively demonstrates the ring orients during translocation with the N-terminal domain leading, indicating that the translocation activity could also provide the physical basis of replication initiation where a double-hexamer idly encircling double-stranded DNA transforms to single-hexamers that encircle only one strand. In this mechanism, each strand binds to the N-terminal tier of one hexamer and the AAA+ tier of the other hexamer such that one ring pulls on the other, aligning equivalent interfaces to enable each hexamer to pull its translocation strand outside of the opposing hexamer.

Suggested Citation

  • Martin Meagher & Leslie B. Epling & Eric J. Enemark, 2019. "DNA translocation mechanism of the MCM complex and implications for replication initiation," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11074-3
    DOI: 10.1038/s41467-019-11074-3
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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. Matthew Day & Bilal Tetik & Milena Parlak & Yasser Almeida-Hernández & Markus Räschle & Farnusch Kaschani & Heike Siegert & Anika Marko & Elsa Sanchez-Garcia & Markus Kaiser & Isabel A. Barker & Laure, 2024. "TopBP1 utilises a bipartite GINS binding mode to support genome replication," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Ananya Acharya & Hélène Bret & Jen-Wei Huang & Martin Mütze & Martin Göse & Vera Maria Kissling & Ralf Seidel & Alberto Ciccia & Raphaël Guérois & Petr Cejka, 2024. "Mechanism of DNA unwinding by MCM8-9 in complex with HROB," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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