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The **guanine N7 position** in nuclear DNA is the most nucleophilic site on the guanine base, making it highly susceptible to modification by alkylating mutagens, carcinogens, and some anticancer drugs[1][2]. Modification of guanine at N7 does not disrupt standard Watson-Crick base pairing, but chemical adducts at this site are chemically unstable and can result in secondary DNA lesions, notably apurinic sites and ring-opened FAPy derivatives, which are more mutagenic[2]. The N7-guanine adducts serve as robust biomarkers for DNA exposure to alkylating agents and environmental carcinogens but are generally considered to have low direct biological significance in mutagenesis compared to other DNA lesions[2]. Bulky adducts or crosslinks induced at N7 can block DNA replication, trigger repair pathways, and promote apoptosis, underlying the cytotoxic activity of certain chemotherapy drugs[1][5]. Due to this role, damage at the N7 position underlies both the therapeutic and toxic effects of various alkylating agents and heavy metal-containing chemotherapeutics[1][5].
Alkylation at N7 (chemical addition of alkyl groups to the N7 position, leading to DNA base adducts and disruption of replication and repair); DNA crosslinking (formation of DNA-DNA or DNA-protein crosslinks via modification at the guanine N7 position)
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