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DNA oxidation is the process of oxidative damage of deoxyribonucleic acid.As described in detail by Burrows et al., [1] 8-oxo-2'-deoxyguanosine (8-oxo-dG) is the most common oxidative lesion observed in duplex DNA because guanine has a lower one-electron reduction potential than the other nucleosides in DNA.
The emergence of Earth's oxygen-rich atmosphere (known as the "oxygen catastrophe") due to photosynthetic organisms, as well as the presence of potentially damaging free radicals in the cell due to oxidative phosphorylation, necessitated the evolution of DNA repair mechanisms that act specifically to counter the types of damage induced by ...
More than 100 types of oxidative DNA damage have been characterized, and 8-oxodG constitutes about 5% of the steady state oxidative damages in DNA. [18] Helbock et al. [ 14 ] estimated that there were 24,000 steady state oxidative DNA adducts per cell in young rats and 66,000 adducts per cell in old rats.
Normal cellular defense mechanisms destroy most of these. Repair of oxidative damages to DNA is frequent and ongoing, largely keeping up with newly induced damages. In rat urine, about 74,000 oxidative DNA adducts per cell are excreted daily. [27] There is also a steady state level of oxidative damages in the DNA of a cell.
It is involved in oxidative DNA damage repair and is part of the base excision repair pathway. The enzyme excises adenine bases from the DNA backbone at sites where adenine is inappropriately paired with guanine, cytosine, or 8-oxo-7,8-dihydroguanine, a common form of oxidative DNA damage. The protein is localized to the nucleus and mitochondria.
Hydroxyl radicals can attack the deoxyribose DNA backbone and bases, potentially causing a plethora of lesions that can be cytotoxic or mutagenic. Cells have developed complex and efficient repair mechanisms to fix the lesions. In the case of free radical attack on DNA, base-excision repair is the repair mechanism used. Hydroxyl radical ...
In humans, it is primarily repaired by DNA glycosylase OGG1. It can be caused by ionizing radiation, in connection with oxidative metabolism. 8-oxoG (syn) in a Hoogsteen base pair with dA (anti) 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.
Mitochondrial ROS attack DNA readily, generating a variety of DNA damages such as oxidized bases and strand breaks. The major mechanism that cells use to repair oxidized bases such as 8-hydroxyguanine, formamidopyrimidine and 5-hydroxyuracil is base excision repair (BER). [14] BER occurs in both the cell nucleus and in mitochondria.