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Can I read DNA interstrand cross-links induced by the major oxidative adenine lesion 7,8-dihydro-8-oxoadenine on EtoBox?

DNA interstrand cross-links induced by the major oxidative adenine lesion 7,8-dihydro-8-oxoadenine by Rozelle, Aaron L. (author);Cheun, Young (author);Vilas, Caroline K. (author);Koag, Myong-Chul (author);Lee, Seongmin (author) is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is DNA interstrand cross-links induced by the major oxidative adenine lesion 7,8-dihydro-8-oxoadenine about?

## Abstract Oxidative damage to DNA generates 7,8-dihydro-8-oxoguanine (oxoG) and 7,8-dihydro-8-oxoadenine (oxoA) as two major lesions. Despite the comparable prevalence of these lesions, the biological effects of oxoA remain poorly characterized. Here we report the discovery of a class of DNA interstrand cross-links (ICLs) involving oxidized nucleobases. Under oxidative conditions, oxoA, but not oxoG, readily reacts with an opposite base to produce ICLs, highlighting a latent alkylating nature of oxoA. Reactive halogen species, one-electron oxidants, and the myeloperoxidase/H~2~O~2~/Cl^−^ system induce oxoA ICLs, suggesting that oxoA-mediated cross-links may arise endogenously. Nucleobase analog studies suggest C2-oxoA is covalently linked to N2-guanine and N3-adenine for the oxoA-G and oxoA-A ICLs, respectively. The oxoA ICLs presumably form via the oxidative activation of oxoA followed by the nucleophilic attack by an opposite base. Our findings provide insights into oxoA-mediated mutagenesis and contribute towards investigations of oxidative stress-induced ICLs and oxoA-based latent alkylating agents.

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Author
Rozelle, Aaron L. (author);Cheun, Young (author);Vilas, Caroline K. (author);Koag, Myong-Chul (author);Lee, Seongmin (author)
Publisher
Springer Science and Business Media LLC
Published
2021
Language
EN
Field
Biochemistry, Genetics and Molecular Biology (Life Sciences)