Japan Agency for Medical Research and Development (AMED)
JP24ama121002
日本
Japan Agency for Medical Research and Development (AMED)
JP24ama121009
日本
引用
ジャーナル: Nat Commun / 年: 2025 タイトル: Structural basis of cyclobutane pyrimidine dimer recognition by UV-DDB in the nucleosome. 著者: Syota Matsumoto / Yoshimasa Takizawa / Mitsuo Ogasawara / Kana Hashimoto / Lumi Negishi / Wenjie Xu / Haruna Tachibana / Junpei Yamamoto / Shigenori Iwai / Kaoru Sugasawa / Hitoshi Kurumizaka / 要旨: 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 ...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.