8-oxo-2’-deoxyguanosine (OdG) is a promutagenic lesion that arises from a reaction between 2’-deoxyguanosine (dG) and reactive oxygen species. OdG can base pair with either 2’-deoxycytidine (dC) or 2’-deoxyadenosine (dA), the latter of which causes dG to dT transversions that may be responsible for the link between OdG and aging, cancer, lupus, and rheumatoid arthritis. In this study, the mutagenicity of OdG was investigated with two A-family polymerases, the large fragment of Pol I from Bacillus stearothermophilus (BF) and a Klenow-Fragment (KF) analog of Taq DNA polymerase from Thermus aquaticus (KT), both of which lack any 3’-exonuclease activity. Previous studies with A-family polymerases have determined that potential steric clashing between a major groove amino acid (I716 in BF and M672 in KT) and the C2 and/or C8 positions of a template OdG influences the efficiency of dCTP or dATP incorporation, consequently effecting the mutagenic potential of OdG. The activity of dCTP and dATP incorporations opposite OdG and eight of its analogues were examined with wild-type BF and KT and compared with data from I716M and I716A BF, as well as M672A and M672I KT to better understand the effects of major groove clashing on OdG mutagenicity.

The influence of a major groove amino acid on the mutagenic potential of 8-oxo-2’-deoxyguanosine with A-family polymerases

256th National Meeting (2018)

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