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DNA damage detection in nucleosomes involves DNA register shifting

Author

Listed:
  • Syota Matsumoto

    (Friedrich Miescher Institute for Biomedical Research
    University of Basel)

  • Simone Cavadini

    (Friedrich Miescher Institute for Biomedical Research
    University of Basel)

  • Richard D. Bunker

    (Friedrich Miescher Institute for Biomedical Research
    University of Basel)

  • Ralph S. Grand

    (Friedrich Miescher Institute for Biomedical Research
    University of Basel)

  • Alessandro Potenza

    (Friedrich Miescher Institute for Biomedical Research
    University of Basel)

  • Julius Rabl

    (Friedrich Miescher Institute for Biomedical Research
    University of Basel)

  • Junpei Yamamoto

    (Osaka University)

  • Andreas D. Schenk

    (Friedrich Miescher Institute for Biomedical Research
    University of Basel)

  • Dirk Schübeler

    (Friedrich Miescher Institute for Biomedical Research
    University of Basel)

  • Shigenori Iwai

    (Osaka University)

  • Kaoru Sugasawa

    (Kobe University)

  • Hitoshi Kurumizaka

    (Institute for Quantitative Biosciences, The University of Tokyo
    Waseda University)

  • Nicolas H. Thomä

    (Friedrich Miescher Institute for Biomedical Research
    University of Basel)

Abstract

Access to DNA packaged in nucleosomes is critical for gene regulation, DNA replication and DNA repair. In humans, the UV-damaged DNA-binding protein (UV-DDB) complex detects UV-light-induced pyrimidine dimers throughout the genome; however, it remains unknown how these lesions are recognized in chromatin, in which nucleosomes restrict access to DNA. Here we report cryo-electron microscopy structures of UV-DDB bound to nucleosomes bearing a 6–4 pyrimidine–pyrimidone dimer or a DNA-damage mimic in various positions. We find that UV-DDB binds UV-damaged nucleosomes at lesions located in the solvent-facing minor groove without affecting the overall nucleosome architecture. In the case of buried lesions that face the histone core, UV-DDB changes the predominant translational register of the nucleosome and selectively binds the lesion in an accessible, exposed position. Our findings explain how UV-DDB detects occluded lesions in strongly positioned nucleosomes, and identify slide-assisted site exposure as a mechanism by which high-affinity DNA-binding proteins can access otherwise occluded sites in nucleosomal DNA.

Suggested Citation

  • Syota Matsumoto & Simone Cavadini & Richard D. Bunker & Ralph S. Grand & Alessandro Potenza & Julius Rabl & Junpei Yamamoto & Andreas D. Schenk & Dirk Schübeler & Shigenori Iwai & Kaoru Sugasawa & Hit, 2019. "DNA damage detection in nucleosomes involves DNA register shifting," Nature, Nature, vol. 571(7763), pages 79-84, July.
  • Handle: RePEc:nat:nature:v:571:y:2019:i:7763:d:10.1038_s41586-019-1259-3
    DOI: 10.1038/s41586-019-1259-3
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    Cited by:

    1. Namrata Kumar & Arjan F. Theil & Vera Roginskaya & Yasmin Ali & Michael Calderon & Simon C. Watkins & Ryan P. Barnes & Patricia L. Opresko & Alex Pines & Hannes Lans & Wim Vermeulen & Bennett Houten, 2022. "Global and transcription-coupled repair of 8-oxoG is initiated by nucleotide excision repair proteins," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Charlotte Blessing & Katja Apelt & Diana Heuvel & Claudia Gonzalez-Leal & Magdalena B. Rother & Melanie Woude & Román González-Prieto & Adi Yifrach & Avital Parnas & Rashmi G. Shah & Tia Tyrsett Kuo &, 2022. "XPC–PARP complexes engage the chromatin remodeler ALC1 to catalyze global genome DNA damage repair," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Anna Sefer & Eleni Kallis & Tobias Eilert & Carlheinz Röcker & Olga Kolesnikova & David Neuhaus & Sebastian Eustermann & Jens Michaelis, 2022. "Structural dynamics of DNA strand break sensing by PARP-1 at a single-molecule level," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Tyler M. Weaver & Nicole M. Hoitsma & Jonah J. Spencer & Lokesh Gakhar & Nicholas J. Schnicker & Bret D. Freudenthal, 2022. "Structural basis for APE1 processing DNA damage in the nucleosome," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    5. Corina Maritz & Reihaneh Khaleghi & Michelle N. Yancoskie & Sarah Diethelm & Sonja Brülisauer & Natalia Santos Ferreira & Yang Jiang & Shana J. Sturla & Hanspeter Naegeli, 2023. "ASH1L-MRG15 methyltransferase deposits H3K4me3 and FACT for damage verification in nucleotide excision repair," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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