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Recognition of hemi-methylated DNA by the SRA protein UHRF1 by a base-flipping mechanism

Author

Listed:
  • Kyohei Arita

    (Graduate School of Engineering, Kyoto University)

  • Mariko Ariyoshi

    (Graduate School of Engineering, Kyoto University)

  • Hidehito Tochio

    (Graduate School of Engineering, Kyoto University
    Japan Science and Technology Agency, CREST, 4-1-18, Honcho, Kawaguchi-shi, Saitama 332-0012, Japan)

  • Yusuke Nakamura

    (Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan)

  • Masahiro Shirakawa

    (Graduate School of Engineering, Kyoto University
    Japan Science and Technology Agency, CREST, 4-1-18, Honcho, Kawaguchi-shi, Saitama 332-0012, Japan
    RIKEN, Yokohama Institute, Suehirocho, Tsurumi, Yokohama 230-0045, Japan)

Abstract

Keeping DNA methylation on track DNA methylation is a key epigenetic process and the faithful maintenance of DNA methylation patterns is essential to the wellbeing of mammalian cells. This means that cells need a mechanism to identify the partially methylated version of CpG once a new DNA strand has been replicated or repaired, so that it can be further methylated by the DNA methyltransferase, DNMT1. As part of this process the protein UHRF1 (or Np95/ICBP90) facilitates the loading of DNMT1 onto the hemimethylated CpG sequences during DNA replication. Three papers in this issue describe crystal structures of the SRA domain of UHRF1 bound to DNA containing a hemi-methylated CpG site. The structures show that methyl-cytosine is flipped out of the DNA helix and inserted into a binding pocket on the SRA domain.

Suggested Citation

  • Kyohei Arita & Mariko Ariyoshi & Hidehito Tochio & Yusuke Nakamura & Masahiro Shirakawa, 2008. "Recognition of hemi-methylated DNA by the SRA protein UHRF1 by a base-flipping mechanism," Nature, Nature, vol. 455(7214), pages 818-821, October.
    • Handle: RePEc:nat:nature:v:455:y:2008:i:7214:d:10.1038_nature07249
    DOI: 10.1038/nature07249
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    Cited by:

    1. Kosuke Yamaguchi & Xiaoying Chen & Brianna Rodgers & Fumihito Miura & Pavel Bashtrykov & Frédéric Bonhomme & Catalina Salinas-Luypaert & Deis Haxholli & Nicole Gutekunst & Bihter Özdemir Aygenli & Lau, 2024. "Non-canonical functions of UHRF1 maintain DNA methylation homeostasis in cancer cells," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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