Purine bases, oxidative damage

Next, some typical examples will be presented of how a DNA-electrochemical biosensor is appropriate to investigate the DNA damage caused by different types of substances, such as the antioxidant agent quercetin (Scheme 20.1), an anticancer drug adriamycin (Scheme 20.2) and nitric oxide. In all cases, the dsDNA damage is detected by changes in the electrochemical behaviour of the immobilized dsDNA, specifically through modifications of the purinic base oxidation peak current [3,5,40]. 

The bacterial formamidopyrimidine-DNA glycosylase (alias Fpg or MutM) is a bifunctional base-repair enzyme (DNA glycosylase/AP lyase) that removes a wide range of oxidized purines from oxidatively damaged DNA. The crystal structures of the Fpg (MutM) enzymes from Thermus thermophilus, Lactococcus lactis Escherichia coli Bacillus stearothermophilus and the sequence similar endonuclease VIII (Nei) from E. all share the same... 

Both NER and BER forms of excision repair remove a great variety of defects, many of which are a result of oxidative damage.657 720 Most prominent among these is 7,8-dihydro-8-oxoguanine (8-OG), which is able to base pair with either cytosine (with normal Watson-Crick hydrogen bonding) or with adenine, which will yield a purine-purine mismatch and aC G —> A T transversion mutation (Eq. 27-24), a frequent mutation in human cancers.721 722... 

The damage to immobilised DNA causes the appearance of oxidation peaks from DNA guanine and adenine purine bases which should always be detected. In the case of occurrence of DNA oxidative damage, the oxidation peaks from the biomarkers for oxidative damage, 8-oxoGua or 2,8-oxoAde, should be evaluated. 

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