Alkylating reagents cause damage to DNA (mainly at O6-G (Guanine), O4-T (Thymine) and O2-T positions in DNA) similar to that induced by ultraviolet irradiation. The bases altered by these reagents are primarily purines (phosphate oxygen is also targets), and the spectrum of products formed varies with the reagent used. An unusual form of DNA repair involving active reversal of DNA damage is present in mammalian cells to correct such miscoding alkylation lesion (Ref.1). The most highly mutagenic of these products is O6-MeG (O6-Methylguanine), which has a very high probability of pairing with thymine when the modified strand replicates. O6-MeG is generated endogenously in small amounts by reactive cellular catabolites.
Two major pathways exist in mammalian cells for the removal and [...]