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. 2014 Jul 15;15(7):12543–12557. doi: 10.3390/ijms150712543

Figure 2.

Figure 2

Mutagenesis caused by 8-oxoguanine and mammalian defense systems. In the mutagenesis pathway, 8-oxoguanine (GO) accumulates in DNA, via the incorporation of 8-oxo-dGTP from the nucleotide pool or because of direct oxidation of DNA. This increases the occurrence of A:T to C:G or G:C to T:A transversion mutations after two rounds of replication. Red line: mutagenic pathway. In the defense systems, MTH1 hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP and pyrophosphate. 8-oxo-dGMP is further converted to nucleoside, 8-oxodeozyguanosine (8-oxo-dG), thus avoiding their incorporation into DNA. 8-oxoG DNA glycosylase (OGG1) removes 8-oxoG to initiate base excision repair (BER). OGG1 preferentially excises 8-oxoG opposite cytosine. MutY homolog (MUTYH) excises the adenine inserted opposite 8-oxoG in the template strand. Once cytosine is inserted opposite 8-oxoG during the BER initiated by MUTYH, OGG1 can remove the 8-oxoG residue opposite cytosine. However, adenine can be reinserted opposite 8-oxoG during BER (dashed red line). In mammals, the mismatch repair machinery recognizes 8-oxoG opposite adenine in template DNA and excises the 8-oxoG containing nascent strand (green line). OGG1 may enhance A to C transversion if it excises 8-oxoG opposite cytosine that had been inserted opposite 8-oxoG paired with the adenine in the template DNA (dashed blue line). Blue lines: BER pathways. Modified from Ref. [6].