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Structural basis of asymmetric DNA methylation and ATP-triggered long-range diffusion by EcoP15I

Author

Listed:
  • Yogesh K. Gupta

    (Icahn School of Medicine at Mount Sinai)

  • Siu-Hong Chan

    (New England Biolabs Inc.)

  • Shuang-yong Xu

    (New England Biolabs Inc.)

  • Aneel K. Aggarwal

    (Icahn School of Medicine at Mount Sinai)

Abstract

Type III R–M enzymes were identified >40 years ago and yet there is no structural information on these multisubunit enzymes. Here we report the structure of a Type III R–M system, consisting of the entire EcoP15I complex (Mod2Res1) bound to DNA. The structure suggests how ATP hydrolysis is coupled to long-range diffusion of a helicase on DNA, and how a dimeric methyltransferase functions to methylate only one of the two DNA strands. We show that the EcoP15I motor domains are specifically adapted to bind double-stranded DNA and to facilitate DNA sliding via a novel ‘Pin’ domain. We also uncover unexpected ‘division of labour’, where one Mod subunit recognizes DNA, while the other Mod subunit methylates the target adenine—a mechanism that may extend to adenine N6 RNA methylation in mammalian cells. Together the structure sheds new light on the mechanisms of both helicases and methyltransferases in DNA and RNA metabolism.

Suggested Citation

  • Yogesh K. Gupta & Siu-Hong Chan & Shuang-yong Xu & Aneel K. Aggarwal, 2015. "Structural basis of asymmetric DNA methylation and ATP-triggered long-range diffusion by EcoP15I," Nature Communications, Nature, vol. 6(1), pages 1-10, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8363
    DOI: 10.1038/ncomms8363
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    Cited by:

    1. Daniel Ramírez Montero & Humberto Sánchez & Edo Veen & Theo Laar & Belén Solano & John F. X. Diffley & Nynke H. Dekker, 2023. "Nucleotide binding halts diffusion of the eukaryotic replicative helicase during activation," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Jiyun Chen & Rong Hu & Ying Chen & Xiaofeng Lin & Wenwen Xiang & Hong Chen & Canglin Yao & Liang Liu, 2022. "Structural basis for MTA1c-mediated DNA N6-adenine methylation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Richard Quintana-Feliciano & Jithesh Kottur & Mi Ni & Rikhia Ghosh & Leslie Salas-Estrada & Goran Ahlsen & Olga Rechkoblit & Lawrence Shapiro & Marta Filizola & Gang Fang & Aneel K. Aggarwal, 2024. "Burkholderia cenocepacia epigenetic regulator M.BceJIV simultaneously engages two DNA recognition sequences for methylation," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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