7E8I

Structural insight into BRCA1-BARD1 complex recruitment to damaged chromatin

7E8I の概要

• エントリーDOI: 10.2210/pdb7e8i/pdb
• EMDBエントリー: 31020
• 分子名称: DNA (145-MER), Histone H3, Histone H4, ... (8 entities in total)
• 機能のキーワード: brca1, nucleosome, dna damage, chromatin, bard1, nuclear protein
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 247503.23

構造登録者

Dai, Y.,Dai, L.,Zhou, Z. (登録日: 2021-03-01, 公開日: 2021-06-30, 最終更新日: 2025-07-02)

主引用文献

Dai, L.,Dai, Y.,Han, J.,Huang, Y.,Wang, L.,Huang, J.,Zhou, Z.
Structural insight into BRCA1-BARD1 complex recruitment to damaged chromatin.
Mol.Cell, 81:2765-2777.e6, 2021

PubMed Abstract: The BRCA1-BARD1 complex directs the DNA double-strand break (DSB) repair pathway choice to error-free homologous recombination (HR) during the S-G2 stages. Targeting BRCA1-BARD1 to DSB-proximal sites requires BARD1-mediated nucleosome interaction and histone mark recognition. Here, we report the cryo-EM structure of BARD1 bound to a ubiquitinated nucleosome core particle (NCP) at 3.1 Å resolution and illustrate how BARD1 simultaneously recognizes the DNA damage-induced mark H2AK15ub and DNA replication-associated mark H4K20me0 on the nucleosome. In vitro and in vivo analyses reveal that the BARD1-NCP complex is stabilized by BARD1-nucleosome interaction, BARD1-ubiquitin interaction, and BARD1 ARD domain-BARD1 BRCT domain interaction, and abrogating these interactions is detrimental to HR activity. We further identify multiple disease-causing BARD1 mutations that disrupt BARD1-NCP interactions and hence impair HR. Together, this study elucidates the mechanism of BRCA1-BARD1 complex recruitment and retention by DSB-flanking nucleosomes and sheds important light on cancer therapeutic avenues.

PubMed: 34102105
DOI: 10.1016/j.molcel.2021.05.010

実験手法

ELECTRON MICROSCOPY (3.1 Å)