N7guanine

N7-guanine refers to a DNA base modification in which an alkyl or other substituent is attached to the nitrogen at position 7 (N7) of the imidazole ring of guanine. The resulting N7-alkylguanine adducts are among the most common guanine lesions formed when cells are exposed to alkylating agents, such as methylating or ethylating chemicals.

Formation and significance: Alkylating agents donate an alkyl group to the N7 position of guanine in genomic DNA, generating N7-guanine adducts. These lesions are frequently detected after exposure to compounds such as methylating agents and nitrosamines, making them useful biomarkers of exposure. N7-guanine adducts are typically abundant but chemically unstable and tend to depurinate, creating abasic sites in DNA that can destabilize the genome if not repaired.

Repair and consequences: The primary cellular response to N7-guanine adducts is base excision repair, which processes abasic sites and helps maintain DNA integrity. Although N7-guanine lesions themselves are generally considered less mutagenic than other alkylation products (notably O6-alkylguanine), their spontaneous loss via depurination and subsequent processing can contribute to replication errors or strand breaks if the repair process encounters obstacles.

Detection and applications: Researchers detect N7-guanine adducts using techniques such as liquid chromatography–mass spectrometry and immunoassays, often after DNA hydrolysis. Because of their high frequency and correlation with alkylating exposure, these adducts serve as practical biomarkers in toxicology, pharmacology, and environmental health studies.

See also: O6-alkylguanine, DNA adducts, base excision repair.