7U50

APE1 bound to a nucleosome core particle with AP-site at SHL-6

7U50 の概要

• エントリーDOI: 10.2210/pdb7u50/pdb
• EMDBエントリー: 26336
• 分子名称: Histone H3.2, Histone H4, Histone H2A type 1, ... (7 entities in total)
• 機能のキーワード: nucleosome, dna damage, dna repair, dna binding protein, 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: 11
• 化学式量合計: 234857.05

構造登録者

Weaver, T.M.,Freudenthal, B.D. (登録日: 2022-03-01, 公開日: 2022-09-07, 最終更新日: 2024-06-12)

主引用文献

Weaver, T.M.,Hoitsma, N.M.,Spencer, J.J.,Gakhar, L.,Schnicker, N.J.,Freudenthal, B.D.
Structural basis for APE1 processing DNA damage in the nucleosome.
Nat Commun, 13:5390-5390, 2022

PubMed Abstract: Genomic DNA is continually exposed to endogenous and exogenous factors that promote DNA damage. Eukaryotic genomic DNA is packaged into nucleosomes, which present a barrier to accessing and effectively repairing DNA damage. The mechanisms by which DNA repair proteins overcome this barrier to repair DNA damage in the nucleosome and protect genomic stability is unknown. Here, we determine how the base excision repair (BER) endonuclease AP-endonuclease 1 (APE1) recognizes and cleaves DNA damage in the nucleosome. Kinetic assays determine that APE1 cleaves solvent-exposed AP sites in the nucleosome with 3 - 6 orders of magnitude higher efficiency than occluded AP sites. A cryo-electron microscopy structure of APE1 bound to a nucleosome containing a solvent-exposed AP site reveal that APE1 uses a DNA sculpting mechanism for AP site recognition, where APE1 bends the nucleosomal DNA to access the AP site. Notably, additional biochemical and structural characterization of occluded AP sites identify contacts between the nucleosomal DNA and histone octamer that prevent efficient processing of the AP site by APE1. These findings provide a rationale for the position-dependent activity of BER proteins in the nucleosome and suggests the ability of BER proteins to sculpt nucleosomal DNA drives efficient BER in chromatin.

PubMed: 36104361
DOI: 10.1038/s41467-022-33057-7

実験手法

ELECTRON MICROSCOPY (3.4 Å)