6R93

Cryo-EM structure of NCP-6-4PP

6R93 の概要

• エントリーDOI: 10.2210/pdb6r93/pdb
• EMDBエントリー: 4767
• 分子名称: Human alpha-satellite DNA (145-MER), Human alpha-satellite DNA (145-MER) with a 6-4PP at positions 95-96, Histone H3.1, ... (6 entities in total)
• 機能のキーワード: dna damage, nucleosome, 6-4 photoproduct, dna
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 201927.49

構造登録者

Matsumoto, S.,Cavadini, S.,Bunker, R.D.,Thoma, N.H. (登録日: 2019-04-02, 公開日: 2019-06-12, 最終更新日: 2024-05-22)

主引用文献

Matsumoto, S.,Cavadini, S.,Bunker, R.D.,Grand, R.S.,Potenza, A.,Rabl, J.,Yamamoto, J.,Schenk, A.D.,Schubeler, D.,Iwai, S.,Sugasawa, K.,Kurumizaka, H.,Thoma, N.H.
DNA damage detection in nucleosomes involves DNA register shifting.
Nature, 571:79-84, 2019

PubMed Abstract: Access to DNA packaged in nucleosomes is critical for gene regulation, DNA replication and DNA repair. In humans, the UV-damaged DNA-binding protein (UV-DDB) complex detects UV-light-induced pyrimidine dimers throughout the genome; however, it remains unknown how these lesions are recognized in chromatin, in which nucleosomes restrict access to DNA. Here we report cryo-electron microscopy structures of UV-DDB bound to nucleosomes bearing a 6-4 pyrimidine-pyrimidone dimer or a DNA-damage mimic in various positions. We find that UV-DDB binds UV-damaged nucleosomes at lesions located in the solvent-facing minor groove without affecting the overall nucleosome architecture. In the case of buried lesions that face the histone core, UV-DDB changes the predominant translational register of the nucleosome and selectively binds the lesion in an accessible, exposed position. Our findings explain how UV-DDB detects occluded lesions in strongly positioned nucleosomes, and identify slide-assisted site exposure as a mechanism by which high-affinity DNA-binding proteins can access otherwise occluded sites in nucleosomal DNA.

PubMed: 31142837
DOI: 10.1038/s41586-019-1259-3

実験手法

ELECTRON MICROSCOPY (4 Å)