8JND

The cryo-EM structure of the nonameric RAD51 ring bound to the nucleosome with the linker DNA binding

8JND の概要

• エントリーDOI: 10.2210/pdb8jnd/pdb
• EMDBエントリー: 36442
• 分子名称: Histone H3.1, Histone H4, Histone H2A type 1-B/E, ... (7 entities in total)
• 機能のキーワード: nucleosome, recombinase, dna binding protein-dna complex, dna binding protein/dna
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 19
• 化学式量合計: 543093.33

構造登録者

Shioi, T.,Hatazawa, S.,Ogasawara, M.,Takizawa, Y.,Kurumizaka, H. (登録日: 2023-06-06, 公開日: 2024-03-27, 最終更新日: 2024-05-08)

主引用文献

Shioi, T.,Hatazawa, S.,Oya, E.,Hosoya, N.,Kobayashi, W.,Ogasawara, M.,Kobayashi, T.,Takizawa, Y.,Kurumizaka, H.
Cryo-EM structures of RAD51 assembled on nucleosomes containing a DSB site.
Nature, 628:212-220, 2024

PubMed Abstract: RAD51 is the central eukaryotic recombinase required for meiotic recombination and mitotic repair of double-strand DNA breaks (DSBs). However, the mechanism by which RAD51 functions at DSB sites in chromatin has remained elusive. Here we report the cryo-electron microscopy structures of human RAD51-nucleosome complexes, in which RAD51 forms ring and filament conformations. In the ring forms, the N-terminal lobe domains (NLDs) of RAD51 protomers are aligned on the outside of the RAD51 ring, and directly bind to the nucleosomal DNA. The nucleosomal linker DNA that contains the DSB site is recognized by the L1 and L2 loops-active centres that face the central hole of the RAD51 ring. In the filament form, the nucleosomal DNA is peeled by the RAD51 filament extension, and the NLDs of RAD51 protomers proximal to the nucleosome bind to the remaining nucleosomal DNA and histones. Mutations that affect nucleosome-binding residues of the RAD51 NLD decrease nucleosome binding, but barely affect DNA binding in vitro. Consistently, yeast Rad51 mutants with the corresponding mutations are substantially defective in DNA repair in vivo. These results reveal an unexpected function of the RAD51 NLD, and explain the mechanism by which RAD51 associates with nucleosomes, recognizes DSBs and forms the active filament in chromatin.

PubMed: 38509361
DOI: 10.1038/s41586-024-07196-4

実験手法

ELECTRON MICROSCOPY (3.66 Å)