2025-11-11 東京大学,科学技術振興機構,神戸大学,大阪大学
ChIP-CryoEM法によるUV-DDBタンパク質の可視化の概要
<関連情報>
- https://www.iqb.u-tokyo.ac.jp/pressrelease/251111/
- https://www.nature.com/articles/s41467-025-65486-5
ヌクレオソームにおけるUV-DDBによるシクロブタンピリミジン二量体認識の構造的基盤 Structural basis of cyclobutane pyrimidine dimer recognition by UV-DDB in the nucleosome
Syota Matsumoto,Yoshimasa Takizawa,Mitsuo Ogasawara,Kana Hashimoto,Lumi Negishi,Wenjie Xu,Haruna Tachibana,Junpei Yamamoto,Shigenori Iwai,Kaoru Sugasawa & Hitoshi Kurumizaka
Nature Communications Published:11 November 2025
DOI:https://doi.org/10.1038/s41467-025-65486-5
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.
