Figure 8.

N6-methyl-dATP is incorporated into DNA in an MTH1-dependent manner. DNA was extracted from zebrafish MTH1KO and MTH1WT embryos developed from fertilized zebrafish eggs microinjected with N6-methyl-dATP or left untreated. DNA was analyzed for N6-methyl-dA content using LC-MS/MS. N6-methyl-dA content was normalized to N6-methyldA levels in untreated MTH1KO and MTH1WT zebrafish embryos, respectively. N6-methyl-dATP microinjected MTH1KO zebrafish embryos display a 2-fold higher N6-methyl-dA level compared with untreated embryos, whereas N6-methyl-dA DNA levels in MTH1WT zebrafish did not differ between untreated and N6-methyl-dA–microinjected embryos. This suggests that N6-methyl-dATP is incorporated into DNA and incorporation can be prevented by MTH1. The graph shows mean ± S.D., n = 2.