DNA and Chromosomes
Enzymatic bypass and the structural basis of miscoding opposite the DNA adduct 1,N2-ethenodeoxyguanosine by human DNA translesion polymerase η
Etheno (ε)-adducts, e.g., 1,N2-ε−guanine (1,N2-ε-G) and 1,N6-ε−adenine (1,N6-ε-A), are formed through the reaction of DNA with metabolites of vinyl compounds or with lipid peroxidation products. These lesions are known to be mutagenic, but it is unknown how they lead to errors in DNA replication that are bypassed by DNA polymerases. Here we report the structural basis of misincorporation frequencies across from 1,N2-ε-G by human DNA polymerase (hpol) η. In single-nucleotide insertions opposite the adduct 1,N2-ε-G, hpol η preferentially inserted dGTP, followed by dATP, dTTP, and dCTP.Roles of Residues Arg-61 and Gln-38 of Human DNA Polymerase η in Bypass of Deoxyguanosine and 7,8-Dihydro-8-oxo-2′-deoxyguanosine
Background: Arg-61 and Gln-38 of human DNA polymerase (hpol) η play important roles in the catalytic reaction.Results: Mutations R61M or Q38A/R61A dramatically disrupt the activity of hpol η.Conclusion: Polarized water molecules can mimic and partially compensate for the missing side chains of Arg-61 and Gln-38 in the Q38A/R61A mutant.Significance: The positioning and positive charge of Arg-61 synergistically contribute to the activity of hpol η, with additional effects of Gln-38.
