guanineN7methyltransferases

Guanine N7-methylation refers to a chemical modification at the N7 position of guanine. The term is used for two main contexts: DNA alkylation adducts formed by exposure to methylating agents, and the 7-methylguanosine cap found on eukaryotic mRNA. In DNA, N7-methylguanine (m7G) arises when guanine is methylated by agents such as methyl methanesulfonate, N-nitroso compounds, or temozolomide. It is one of the most common products of DNA alkylation and is typically formed at relatively high frequency after exposure to these agents.

The N7-methylguanine adduct is relatively unstable and readily undergoes depurination, producing abasic sites that can hinder replication and, if left unrepaired, may lead to strand breaks. Because of this, cells rely primarily on base excision repair to remove m7G and restore the DNA sequence. Specific DNA glycosylases recognize alkylated bases and initiate repair, with subsequent processing by AP endonuclease, DNA polymerase, and ligase. Although m7G itself is not highly mutagenic, its persistence or misrepair can contribute to genomic instability when repair is overwhelmed or inaccurate.

Detection and biological relevance: Measurement of m7G adducts serves as a biomarker of exposure to methylating agents in toxicology and pharmacology studies. Analytical methods include high-performance liquid chromatography and tandem mass spectrometry. The adduct’s abundance reflects exposure dose and repair capacity, but its transient nature means it provides a snapshot rather than a cumulative record of exposure.

In RNA biology, the term 7-methylguanosine refers to the cap structure (m7G) at the 5' end of eukaryotic mRNA, which is essential for translation initiation, RNA stability, and processing. This cap is formed by dedicated enzymes and is distinct from the DNA-side N7-methylation discussed above.