Abstract
Purine 5′,8-cyclo-2′-deoxynucleosides (cPu) are tandem-type lesions observed among the DNA purine modifications and identified in mammalian cellular DNA in vivo. These lesions can be present in two diasteroisomeric forms, 5′R and 5′S, for each 2′-deoxyadenosine and 2′-deoxyguanosine moiety. They are generated exclusively by hydroxyl radical attack to 2′-deoxyribose units generating C5′ radicals, followed by cyclization with the C8 position of the purine base. This review describes the main recent achievements in the preparation of the cPu molecular library for analytical and DNA synthesis applications for the studies of the enzymatic recognition and repair mechanisms, their impact on transcription and genetic instability, quantitative determination of the levels of lesions in various types of cells and animal model systems, and relationships between the levels of lesions and human health, disease, and aging, as well as the defining of the detection limits and quantification protocols.
Highlights
It has been shown that pol β wild-type mouse embryonic fibroblast (MEF) cell extracts can generate a significant amount of DNA synthesis products resulting from the bypass of an R-Cyclo-20 -Deoxyadenosine (cdA) and S-cdA lesion located in an open template, i.e., a DNA substrate containing a 1-nt gap or 1-nt gap with a sugar–phosphate residue [84]
Xeroderma pigmentosum (XP) can result from mutations in any of eight within the range of 0–60 Gy, was found to be 0.23 for cdA and 0.35 for cyclo-20 -deoxyguanosine (cdG) in ds-DNA using the method reported in Figure 11 [30], whereas the values of similar experiments were reported to be 14.2 for cdA and 20.1 cdG [105] using direct injection after the enzymatic digestion step without internal standards, which is a ∼60-fold excess for both cdA and cdG
We have summarized the recent work on purine 50,8-cyclo-20 -deoxynucleosides, a subject of growing interest in studies on DNA damage and impact on human health and disease
Summary
Since the start of life on Earth, the human body has lived in an oxidative atmosphere due to the presence of molecular oxygen (dioxygen in its ground triplet state), which plays an immense role in biological processes [1,2]. 3.5 kg of molecular oxygen every day and 2.8%. Of it is utilized to generate free radicals. Superoxide dismutase (SOD) and nitric oxide synthase (NOS). Are two classes of enzymes that control the production of superoxide radical anions (O2 – ) and induce the formation of nitric oxide ( NO) [2]. These two radicals are the progenitors of endogenous reactive The main processes that generate HO radicals are depicted in reactions (1)–(3): the Fenton reaction of H2 O2 , the reduction of HOCl by the superoxide radical anion, and the spontaneous decomposition of protonated ONOO– , respectively [2,3]
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