8VX5

Nucleosome core particle containing an 8-oxoG damage site

Summary for 8VX5

• Entry DOI: 10.2210/pdb8vx5/pdb
• EMDB information: 43608
• Descriptor: Histone H3.2, Histone H4, Histone H2A, ... (6 entities in total)
• Functional Keywords: nucleosome core particle containing 8-oxog dna damage, structural protein-dna complex, structural protein/dna
• Biological source: Xenopus laevis (African clawed frog); More
• Total number of polymer chains: 10
• Total formula weight: 224100.68

Authors

You, Q.,Li, H. (deposition date: 2024-02-03, release date: 2024-10-09)

Primary citation

You, Q.,Feng, X.,Cai, Y.,Baylin, S.B.,Li, H.
Human 8-oxoguanine glycosylase OGG1 binds nucleosome at the dsDNA ends and the super-helical locations.
Commun Biol, 7:1202-1202, 2024

PubMed Abstract: The human glycosylase OGG1 extrudes and excises the oxidized DNA base 8-oxoguanine (8-oxoG) to initiate base excision repair and plays important roles in many pathological conditions such as cancer, inflammation, and neurodegenerative diseases. Previous structural studies have used a truncated protein and short linear DNA, so it has been unclear how full-length OGG1 operates on longer DNA or on nucleosomes. Here we report cryo-EM structures of human OGG1 bound to a 35-bp long DNA containing an 8-oxoG within an unmethylated Cp-8-oxoG dinucleotide as well as to a nucleosome with an 8-oxoG at super-helical location (SHL)-5. The 8-oxoG in the linear DNA is flipped out by OGG1, consistent with previous crystallographic findings with a 15-bp DNA. OGG1 preferentially binds near dsDNA ends at the nucleosomal entry/exit sites. Such preference may underlie the enzyme's function in DNA double-strand break repair. Unexpectedly, we find that OGG1 bends the nucleosomal entry DNA, flips an undamaged guanine, and binds to internal nucleosomal DNA sites such as SHL-5 and SHL+6. We suggest that the DNA base search mechanism by OGG1 may be chromatin context-dependent and that OGG1 may partner with chromatin remodelers to excise 8-oxoG at the nucleosomal internal sites.

PubMed: 39341999
DOI: 10.1038/s42003-024-06919-7

Experimental method

ELECTRON MICROSCOPY (3.3 Å)