A Role for N6-Methyladenine in DNA Damage Repair

Trends Biochem Sci. 2021 Mar;46(3):175-183. doi: 10.1016/j.tibs.2020.09.007. Epub 2020 Oct 16.


The leading cause of mutation due to oxidative damage is 8-oxo-2'-deoxyguanosine (8-oxoG) mispairing with adenine (Ade), which can occur in two ways. First, guanine of a G:C DNA base pair can be oxidized. If not repaired in time, DNA polymerases can mispair Ade with 8-oxoG in the template. This 8-oxoG:A can be repaired by enzymes that remove Ade opposite to template 8-oxoG, or 8-oxoG opposite to Cyt. Second, free 8-oxo-dGTP can be misincorporated by DNA polymerases into DNA opposite template Ade. However, there is no known repair activity that removes 8-oxoG opposite to template Ade. We suggest that a major role of N6-methyladenine in mammalian DNA is minimizing incorporation of 8-oxoG opposite to Ade by DNA polymerases following adduct formation.

Keywords: 8-oxoguanine; DNA adenine methylation; MettL3-MettL14; YTHDC1; single-stranded DNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • DNA Damage
  • DNA Repair*
  • DNA Replication
  • DNA-Directed DNA Polymerase / metabolism
  • Guanine*


  • Guanine
  • DNA-Directed DNA Polymerase