The abundant DNA adduct N ⁷-methyl deoxyguanosine contributes to miscoding during replication by human DNA polymerase η.

ABSTRACT: Aside from abasic sites and ribonucleotides, the DNA adduct N ⁷-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 We found that hpol η and Dpo4 can bypass the N⁷ -CH

SUBMITTER: Njuma OJ 

PROVIDER: S-EPMC6664181 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature