9EOZ

Human OGG1 bound to a nucleosome core particle with 8-oxodGuo lesion at SHL6.0

9EOZ の概要

• エントリーDOI: 10.2210/pdb9eoz/pdb
• EMDBエントリー: 19870
• 分子名称: N-glycosylase/DNA lyase, Histone H4, Histone H3.3, ... (7 entities in total)
• 機能のキーワード: hogg1, 8-oxoguanine, nucleosome, base excision repair, dna binding protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 11
• 化学式量合計: 238227.06

構造登録者

Ren, M.,Gut, F.,Fan, Y.,Hopfner, K.-P.,Zhou, C. (登録日: 2024-03-16, 公開日: 2024-11-06)

主引用文献

Ren, M.,Gut, F.,Fan, Y.,Ma, J.,Shan, X.,Yikilmazsoy, A.,Likhodeeva, M.,Hopfner, K.P.,Zhou, C.
Structural basis for human OGG1 processing 8-oxodGuo within nucleosome core particles.
Nat Commun, 15:9407-9407, 2024

PubMed Abstract: Base excision repair (BER) is initialized by DNA glycosylases, which recognize and flip damaged bases out of the DNA duplex into the enzymes active site, followed by cleavage of the glycosidic bond. Recent studies have revealed that all types of DNA glycosylases repair base lesions less efficiently within nucleosomes, and their repair activity is highly depended on the lesion's location within the nucleosome. To reveal the underlying molecular mechanism of this phenomenon, we determine the 3.1 Å cryo-EM structure of human 8-oxoguanine-DNA glycosylase 1 (hOGG1) bound to a nucleosome core particle (NCP) containing a common oxidative base lesion, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo). Our structural analysis shows that hOGG1 can recognize and flip 8-oxodGuo even within NCPs; however, the interaction between 8-oxodGuo and hOGG1 in a NCP context is weaker than in free DNA due to competition for nucleosomal DNA by the histones. Binding of OGG1 and the flipping of 8-oxodGuo by hOGG1 leads to a partial detachment of DNA from the histone core and a ratchet-like inward movement of nucleosomal DNA. Our findings provide insights into how the dynamic structure of nucleosomes modulate the activity of repair enzymes within chromatin.

PubMed: 39477986
DOI: 10.1038/s41467-024-53811-3

実験手法

ELECTRON MICROSCOPY (3.1 Å)