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The **N7 position of guanine** in double-stranded DNA is the most nucleophilic site among DNA bases and is highly susceptible to modification by endogenous and exogenous alkylating agents[1][2]. Alkylation (or formation of other covalent adducts) at this site yields **N7-guanine adducts**, which are widely used as biomarkers for exposure to carcinogens and anticancer drugs[2]. These adducts are typically **chemically unstable** and can lead to the formation of apurinic (AP) sites upon depurination, potentially resulting in mutations if not correctly repaired. While the N7-guanine adducts themselves are typically not directly mutagenic, their presence and instability play a role in DNA damage response and cellular toxicity. This site in guanine is not a protein or classical molecular target, but is critical to understanding the mechanisms of DNA damage and repair and the biological effects of DNA-reactive chemicals[1][2][6].
Formation of covalent adducts at N7 of guanine leading to DNA crosslinking, base excision, or mispairing
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