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. Author manuscript; available in PMC: 2020 May 1.
Published in final edited form as: DNA Repair (Amst). 2019 Feb 27;77:36–44. doi: 10.1016/j.dnarep.2019.02.014

Figure 1. Pathways that influence uracil accumulation in DNA.

Figure 1.

In de novo dTMP biosynthesis, TYMS transfers a one-carbon unit from 5,10-methylenetetrahydrofolate, onto dUMP, synthesizing dTMP. SHMT1, DHFR, TYMS, and MTHFD1 are SUMOylated and form a lamin-bound nuclear complex at sites of DNA replication and repair. In the salvage pathway, TK1 generates dTMP via phosphorylation of the nucleoside dT. TYMK phosphorylates dTMP, synthesizing dTDP. NDPK phosphorylates dTDP and dUDP, generating dTTP and dUTP, respectively. DNA polymerases incorporate dUTP into DNA. dUTPase dephosphorylates dUTP into dUMP. Spontaneous and enzymatic cytosine deamination by the enzymes AID or APOBEC can lead to U:G mispairs in DNA. Incorporated uracil is excised primarily by UNG, initiating uracil repair. AID, activation induced cytosine deamination; APOBEC, Apolipoprotein B Editing Complex Catalytic Subunit 1; DHFR, dihydrofolate reductase; dUTPase; dUTP phosphorylase; MTHFD1,methylenetetrahydrofolate dehydrogenase 1; NDPK, nucleoside-diphosphate kinase; S, small ubiquitin-related modifier (SUMO), SHMT1, serine hydroxymethyltransferase 1; TK1, thymidine Kinase 1; TYMK, thymidylate kinase; TYMS, dTMP synthase; UNG, uracil N-glycosylase.