8B0A

Cryo-EM structure of ALC1 bound to an asymmetric, site-specifically PARylated nucleosome

8B0A の概要

• エントリーDOI: 10.2210/pdb8b0a/pdb
• 関連するPDBエントリー: 7otq
• EMDBエントリー: 13065 13070 15777
• 分子名称: Chromodomain-helicase-DNA-binding protein 1-like, Histone H3, Histone H4, ... (7 entities in total)
• 機能のキーワード: alc1, chd1l, nucleosome, parylation, adp-ribosylation, post-translational modification, chromatin, 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: 306814.43

構造登録者

Bacic, L.,Gaullier, G.,Deindl, S. (登録日: 2022-09-07, 公開日: 2023-09-20, 最終更新日: 2024-04-03)

主引用文献

Bacic, L.,Gaullier, G.,Mohapatra, J.,Mao, G.,Brackmann, K.,Panfilov, M.,Liszczak, G.,Sabantsev, A.,Deindl, S.
Asymmetric nucleosome PARylation at DNA breaks mediates directional nucleosome sliding by ALC1.
Nat Commun, 15:1000-1000, 2024

PubMed Abstract: The chromatin remodeler ALC1 is activated by DNA damage-induced poly(ADP-ribose) deposited by PARP1/PARP2 and their co-factor HPF1. ALC1 has emerged as a cancer drug target, but how it is recruited to ADP-ribosylated nucleosomes to affect their positioning near DNA breaks is unknown. Here we find that PARP1/HPF1 preferentially initiates ADP-ribosylation on the histone H2B tail closest to the DNA break. To dissect the consequences of such asymmetry, we generate nucleosomes with a defined ADP-ribosylated H2B tail on one side only. The cryo-electron microscopy structure of ALC1 bound to such an asymmetric nucleosome indicates preferential engagement on one side. Using single-molecule FRET, we demonstrate that this asymmetric recruitment gives rise to directed sliding away from the DNA linker closest to the ADP-ribosylation site. Our data suggest a mechanism by which ALC1 slides nucleosomes away from a DNA break to render it more accessible to repair factors.

PubMed: 38307862
DOI: 10.1038/s41467-024-45237-8

実験手法

ELECTRON MICROSCOPY (3 Å)