Fig. 7 | Scientific Reports

Fig. 7

From: Cytotoxic mechanisms of pemetrexed and HDAC inhibition in non-small cell lung cancer cells involving ribonucleotides in DNA

Fig. 7

Model for cytotoxic mechanism of PMX and fluoropyrimidines (5-FdU and 5-FU). TYMS inhibition results in reduced dTTP and increased relative levels of dUTP and rUTP which are incorporated during DNA replication in both mitochondrial and nuclear DNA, forming dU (red) and rU (green) lesions, respectively. PMX mediates oxidative damage while 5-FUMP is incorporated into RNA. The fluorinated deoxy- and the ribonucleotide analogues are also incorporated into mitochondrial and nuclear DNA, as 5-FdUMP and 5-FUMP, respectively. DNA repair proteins or pathways (in blue) excise their indicated DNA lesions. Persistent rU in nuclear DNA may result in cGAS-STING activation.

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