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. 2020 Mar 6;295(15):4761–4772. doi: 10.1074/jbc.RA120.012636

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© 2020 Scaletti et al.

Author's Choice—Final version open access under the terms of the Creative Commons CC-BY license.

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Figure 9. — Potential routes for cellular production and metabolism of N6-methyl-dATP and N6-methyl-ATP. N6-methyl-dATP and N6-methyl-ATP may be produced from N6-methyl-dAMP and N6-methyl-AMP formed upon DNA and RNA degradation, respectively. This may occur through the consecutive actions of adenylate kinase (AK) and nucleoside diphosphate kinase or through nonspecific methylation by S-adenosylmethionine (SAM), the N6-adenosine-methyltransferase METTL3 or N6-adenine–specific DNA methyltransferase 1 (N6AMT1). N6-methyl-dATP and N6-methyl-ATP are hydrolyzed by MTH1 to their corresponding monophosphates and further metabolized by ADAL1 to dIMP and IMP that can then enter the nucleotide salvage pathway. Abbreviations used in the figure: NDPK, nucleoside diphosphate kinase; RNR, ribonucleotide reductase; METTL3, N6-adenosine methyltransferase; N6AMT1, N6-adenine-specific DNA methyltransferase 1.