8-Oxoguanine

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8-Oxoguanine[1]
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MeSH 8-hydroxyguanine
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8-Oxoguanine (8-hydroxyguanine, 8-oxo-Gua, or OH8Gua) is one of the most common DNA lesions resulting from reactive oxygen species[2] modifying guanine, and can result in a mismatched pairing with adenine resulting in G to T and C to A substitutions in the genome.[3] In humans, it is primarily repaired by DNA glycosylase OGG1. It can be caused by ionizing radiation, in connection with oxidative metabolism.

File:8-oxoG forming Hoogsten base pair with dA.svg
8-oxoG (syn) in a Hoogsteen base pair with dA (anti)
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For comparison here is a standard (non-mutagenic) GC base pair with both bases in the anti configuration of the bond between base and sugar.

In body fluids

Increased concentrations of 8-oxoguanine in body fluids have been found to be associated with increased risk of mutagenesis and carcinogenesis.[4][5]

Care must be taken in the assay of 8-oxoguanine due to the ease with which it can be oxidised during extraction and the assay procedure.[6]

Cancer, aging, infertility

The role of the deoxyriboside form of 8-oxoguanine, 8-oxo-2'-deoxyguanosine (abbreviated 8-oxo-dG or 8-OHdG) in cancer and aging also applies to 8-oxoguanine. Oxoguanine glycosylase is employed in the removal of 8-oxoguanine from DNA by the process of base excision repair. As described in oxoguanine glycosylase, deficient expression of this enzyme causes 8-oxoguanine to accumulate in DNA. This accumulation may then lead upon replication of DNA to mutations including some that contribute to carcinogenesis. 8-oxoguanine is usually formed by the interaction of reactive oxygen species (ROS) with the guanine base in DNA under conditions of oxidative stress; as noted in the article about them, such species may have a role in aging and male infertility, and 8-oxoguanine can be used to measure such stress.

References

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  1. 8-hydroxyguanine - Compound Summary, PubChem
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