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Structural basis of cyclobutane pyrimidine dimer recognition by UV-DDB in the nucleosome

Author

Listed:
  • Syota Matsumoto

    (The University of Tokyo)

  • Yoshimasa Takizawa

    (The University of Tokyo
    The University of Tokyo)

  • Mitsuo Ogasawara

    (The University of Tokyo)

  • Kana Hashimoto

    (The University of Tokyo)

  • Lumi Negishi

    (The University of Tokyo)

  • Wenjie Xu

    (The University of Tokyo
    The University of Tokyo)

  • Haruna Tachibana

    (The University of Tokyo
    The University of Tokyo)

  • Junpei Yamamoto

    (Osaka University)

  • Shigenori Iwai

    (Osaka University)

  • Kaoru Sugasawa

    (Kobe University)

  • Hitoshi Kurumizaka

    (The University of Tokyo
    The University of Tokyo
    RIKEN Center for Biosystems Dynamics Research)

Abstract

In mammalian global genomic nucleotide excision repair, UV-DDB plays a central role in recognizing DNA lesions, such as 6-4 photoproducts and cyclobutane pyrimidine dimers, within chromatin. In the present study, we perform cryo-electron microscopy analyses coupled with chromatin-immunoprecipitation to reveal that the cellular UV-DDB binds to UV-damaged DNA lesions in a chromatin unit, the nucleosome, at a position approximately 20 base-pairs from the nucleosomal dyad in human cells. An alternative analysis of the in vitro reconstituted UV-DDB-cyclobutane pyrimidine dimer nucleosome structure demonstrates that the DDB2 subunit of UV-DDB specifically recognizes the cyclobutane pyrimidine dimer lesion at this position on the nucleosome. We also determine the structures of UV-DDB bound to DNA lesions at other positions in purified cellular human nucleosomes. These cellular and reconstituted UV-DDB-nucleosome complex structures provide important evidence for understanding the mechanism by which UV lesions in chromatin are recognized and repaired in mammalian cells.

Suggested Citation

  • Syota Matsumoto & Yoshimasa Takizawa & Mitsuo Ogasawara & Kana Hashimoto & Lumi Negishi & Wenjie Xu & Haruna Tachibana & Junpei Yamamoto & Shigenori Iwai & Kaoru Sugasawa & Hitoshi Kurumizaka, 2025. "Structural basis of cyclobutane pyrimidine dimer recognition by UV-DDB in the nucleosome," Nature Communications, Nature, vol. 16(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65486-5
    DOI: 10.1038/s41467-025-65486-5
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    References listed on IDEAS

    as
    1. Tomoya Kujirai & Junko Kato & Kyoka Yamamoto & Seiya Hirai & Takeru Fujii & Kazumitsu Maehara & Akihito Harada & Lumi Negishi & Mitsuo Ogasawara & Yuki Yamaguchi & Yasuyuki Ohkawa & Yoshimasa Takizawa, 2025. "Multiple structures of RNA polymerase II isolated from human nuclei by ChIP-CryoEM analysis," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    2. Marjo-Riitta Puumalainen & Davor Lessel & Peter Rüthemann & Nina Kaczmarek & Karin Bachmann & Kristijan Ramadan & Hanspeter Naegeli, 2014. "Chromatin retention of DNA damage sensors DDB2 and XPC through loss of p97 segregase causes genotoxicity," Nature Communications, Nature, vol. 5(1), pages 1-10, September.
    3. Yan Han & Alexis A Reyes & Sara Malik & Yuan He, 2020. "Cryo-EM structure of SWI/SNF complex bound to a nucleosome," Nature, Nature, vol. 579(7799), pages 452-455, March.
    4. Karolin Luger & Armin W. Mäder & Robin K. Richmond & David F. Sargent & Timothy J. Richmond, 1997. "Crystal structure of the nucleosome core particle at 2.8 Å resolution," Nature, Nature, vol. 389(6648), pages 251-260, September.
    5. 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.
    6. 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. "Publisher Correction: DNA damage detection in nucleosomes involves DNA register shifting," Nature, Nature, vol. 571(7764), pages 6-6, July.
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