Site-Specific Synthesis of Oligonucleotides Containing 6-Oxo-M₁dG, the Genomic Metabolite of M₁dG, and Liquid Chromatography-Tandem Mass Spectrometry Analysis of Its In Vitro Bypass by Human Polymerase ι.

ABSTRACT: The lipid peroxidation product malondialdehyde and the DNA peroxidation product base-propenal react with dG to generate the exocyclic adduct, M₁dG. This mutagenic lesion has been found in human genomic and mitochondrial DNA. M₁dG in genomic DNA is enzymatically oxidized to 6-oxo-M₁dG, a lesion of currently unknown mutagenic potential. Here, we report the synthesis of an oligonucleotide containing 6-oxo-M₁dG and the results of extension experiments aimed at determining the effect of the 6-oxo-M₁dG lesion on the activity of human polymerase iota (hPol ι). For this purpose, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed to obtain reliable quantitative data on the utilization of poorly incorporated nucleoti

SUBMITTER: Christov PP 

PROVIDER: S-EPMC10518890 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature