9J8W

Cryo-EM structure of NCP-UV-DDB complex containing CPD

Summary for 9J8W

• Entry DOI: 10.2210/pdb9j8w/pdb
• EMDB information: 61243
• Descriptor: Histone H3.1, Histone H4, Histone H2A type 1-B/E, ... (7 entities in total)
• Functional Keywords: dna repair, nucleosome, uv-ddb, dna damage, ddb2, ner, dna binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 11
• Total formula weight: 247263.99

Authors

Matsumoto, S.,Takizawa, Y.,Ogasawara, M.,Hashimoto, K.,Negishi, L.,Xu, W.,Tachibana, H.,Yamamoto, J.,Iwai, S.,Sugasawa, K.,Kurumizaka, H. (deposition date: 2024-08-21, release date: 2025-11-19)

Primary citation

Matsumoto, S.,Takizawa, Y.,Ogasawara, M.,Hashimoto, K.,Negishi, L.,Xu, W.,Tachibana, H.,Yamamoto, J.,Iwai, S.,Sugasawa, K.,Kurumizaka, H.
Structural basis of cyclobutane pyrimidine dimer recognition by UV-DDB in the nucleosome.
Nat Commun, 16:9709-9709, 2025

PubMed 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.

PubMed: 41219227
DOI: 10.1038/s41467-025-65486-5

Experimental method

ELECTRON MICROSCOPY (3.38 Å)