Aside from abasic sites and ribonucleotides, the DNA adduct N7-methyl deoxyguanosine (N7-CH3 dG) is one of the most abundant lesions in mammalian DNA. Because N7-CH3 dG is unstable, leading to deglycosylation and ring-opening, its miscoding potential is not well-understood. Here, we employed a 2′-fluoro isostere approach to synthesize an oligonucleotide containing an analog of this lesion (N7-CH3 2′-F dG) and examined its miscoding potential with four Y-family translesion synthesis DNA polymerases (pols): human pol (hpol) η, hpol κ, and hpol ι and Dpo4 from the archaeal thermophile Sulfolobus solfataricus.
