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TitleStructural basis for human OGG1 processing 8-oxodGuo within nucleosome core particles.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 9407, Year 2024
Publish dateOct 31, 2024
AuthorsMengtian Ren / Fabian Gut / Yilan Fan / Jingke Ma / Xiajing Shan / Aysenur Yikilmazsoy / Mariia Likhodeeva / Karl-Peter Hopfner / Chuanzheng Zhou /
PubMed AbstractBase excision repair (BER) is initialized by DNA glycosylases, which recognize and flip damaged bases out of the DNA duplex into the enzymes active site, followed by cleavage of the glycosidic bond. ...Base excision repair (BER) is initialized by DNA glycosylases, which recognize and flip damaged bases out of the DNA duplex into the enzymes active site, followed by cleavage of the glycosidic bond. Recent studies have revealed that all types of DNA glycosylases repair base lesions less efficiently within nucleosomes, and their repair activity is highly depended on the lesion's location within the nucleosome. To reveal the underlying molecular mechanism of this phenomenon, we determine the 3.1 Å cryo-EM structure of human 8-oxoguanine-DNA glycosylase 1 (hOGG1) bound to a nucleosome core particle (NCP) containing a common oxidative base lesion, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo). Our structural analysis shows that hOGG1 can recognize and flip 8-oxodGuo even within NCPs; however, the interaction between 8-oxodGuo and hOGG1 in a NCP context is weaker than in free DNA due to competition for nucleosomal DNA by the histones. Binding of OGG1 and the flipping of 8-oxodGuo by hOGG1 leads to a partial detachment of DNA from the histone core and a ratchet-like inward movement of nucleosomal DNA. Our findings provide insights into how the dynamic structure of nucleosomes modulate the activity of repair enzymes within chromatin.
External linksNat Commun / PubMed:39477986 / PubMed Central
MethodsEM (single particle)
Resolution3.1 Å
Structure data

19870

9eoz

EMDB-19870, PDB-9eoz:
Human OGG1 bound to a nucleosome core particle with 8-oxodGuo lesion at SHL6.0
Method: EM (single particle) / Resolution: 3.1 Å

Source
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsDNA BINDING PROTEIN / hOGG1 / 8-oxoguanine / nucleosome / base excision repair

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