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TitleHuman 8-oxoguanine glycosylase OGG1 binds nucleosome at the dsDNA ends and the super-helical locations.
Journal, issue, pagesCommun Biol, Vol. 7, Issue 1, Page 1202, Year 2024
Publish dateSep 28, 2024
AuthorsQinglong You / Xiang Feng / Yi Cai / Stephen B Baylin / Huilin Li /
PubMed AbstractThe 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, ...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.
External linksCommun Biol / PubMed:39341999 / PubMed Central
MethodsEM (single particle)
Resolution3.2 - 7.6 Å
Structure data

EMDB-43607, PDB-8vx4:
Human OGG1 bound to a 35-bp DNA with an 8-oxoG in the middle
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-43608, PDB-8vx5:
Nucleosome core particle containing an 8-oxoG damage site
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-43609, PDB-8vx6:
Human OGG1 bound at the nucleosomal DNA entry site
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-43610: Human OGG1 bound at the nucleosomal super helical location -5
Method: EM (single particle) / Resolution: 5.7 Å

EMDB-43611: Human OGG1 bound at the nucleosomal super helical location +6
Method: EM (single particle) / Resolution: 7.6 Å

Source
  • homo sapiens (human)
  • synthetic construct (others)
  • xenopus laevis (African clawed frog)
KeywordsHYDROLASE / LYASE/DNA / Human OGG1 binding at 8-oxoG of a 35 bp DNA duplex / LYASE-DNA complex / STRUCTURAL PROTEIN/DNA / Nucleosome core particle containing 8-oxoG DNA damage / STRUCTURAL PROTEIN-DNA complex / LYASE/STRUCTURAL PROTEIN/DNA / LYASE-STRUCTURAL PROTEIN-DNA complex

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