8-oxo-7,8-dihydroguanine DNA N-glycosylase activity

Definition

Target type: molecularfunction

Catalysis of the removal of 8-oxo-7,8-dihydroguanine bases by cleaving the N-C1' glycosidic bond between the oxidized purine and the deoxyribose sugar. [GOC:mah, PMID:17641464]

8-oxo-7,8-dihydroguanine DNA N-glycosylase activity, also known as MutM in bacteria and OGG1 in eukaryotes, is a crucial DNA repair enzyme that removes the mutagenic and cytotoxic base lesion 8-oxo-7,8-dihydroguanine (8-oxoG) from DNA. 8-oxoG is a major oxidative DNA damage product formed by reactive oxygen species (ROS), which can arise from normal cellular metabolism or environmental exposure to toxins. The accumulation of 8-oxoG can lead to mutations and genomic instability, contributing to aging and cancer development.

The primary function of 8-oxo-7,8-dihydroguanine DNA N-glycosylase is to catalyze the excision of 8-oxoG from the DNA backbone, specifically from the N-glycosidic bond linking the damaged base to deoxyribose sugar. This enzymatic reaction occurs through a two-step mechanism:

1. **Base flipping:** The enzyme recognizes and binds to the damaged DNA sequence, flipping the 8-oxoG base out of the DNA helix. This allows the catalytic domain of the enzyme to access the damaged base.

2. **Glycosidic bond cleavage:** The enzyme then cleaves the glycosidic bond between 8-oxoG and the deoxyribose sugar, releasing the damaged base from the DNA strand.

The resulting abasic site (a site lacking a base) in the DNA is then processed by other DNA repair enzymes, such as AP endonuclease, which cleaves the DNA backbone at the abasic site. Finally, DNA polymerase fills in the gap with the correct nucleotide, and DNA ligase seals the nick, restoring the DNA sequence to its original form.

In addition to its primary function in removing 8-oxoG, 8-oxo-7,8-dihydroguanine DNA N-glycosylase also exhibits a secondary activity:

**8-oxoG-dependent DNA glycosylase activity:** This activity is less efficient than the primary activity and involves the excision of other damaged bases, such as 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) and guanidinohydantoin (Gh), from the DNA. These secondary activities suggest a broader role for the enzyme in DNA repair, beyond simply removing 8-oxoG.

The 8-oxo-7,8-dihydroguanine DNA N-glycosylase activity is essential for maintaining genomic integrity and preventing the accumulation of mutations. Mutations in the genes encoding this enzyme have been linked to various diseases, including cancer and neurodegenerative disorders. This highlights the crucial role of 8-oxo-7,8-dihydroguanine DNA N-glycosylase in human health and underscores the importance of understanding its molecular function.'
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Proteins (2)

Compounds (5)