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TitleStructural basis of cyclobutane pyrimidine dimer recognition by UV-DDB in the nucleosome.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 9709, Year 2025
Publish dateNov 11, 2025
AuthorsSyota Matsumoto / Yoshimasa Takizawa / Mitsuo Ogasawara / Kana Hashimoto / Lumi Negishi / Wenjie Xu / Haruna Tachibana / Junpei Yamamoto / Shigenori Iwai / Kaoru Sugasawa / Hitoshi Kurumizaka /
PubMed AbstractIn 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 ...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.
External linksNat Commun / PubMed:41219227 / PubMed Central
MethodsEM (single particle)
Resolution3.38 - 12.3 Å
Structure data

EMDB-61242: Cryo-EM structure of native NCP-UV-DDB complex
Method: EM (single particle) / Resolution: 12.3 Å

61243

9j8w

EMDB-61243, PDB-9j8w:
Cryo-EM structure of NCP-UV-DDB complex containing CPD
Method: EM (single particle) / Resolution: 3.38 Å

EMDB-61246: Cryo-EM structure of UV-DDB bound to native NCP at SHL+/-2
Method: EM (single particle) / Resolution: 3.78 Å

EMDB-61247: Cryo-EM structure of UV-DDB bound to native NCP at SHL+/-3
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-61248: Cryo-EM structure of UV-DDB bound to native NCP at SHL+/-6
Method: EM (single particle) / Resolution: 3.85 Å

Source
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsDNA BINDING PROTEIN / DNA repair / Nucleosome / UV-DDB / DNA damage / DDB2 / NER

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