dUMP

dUMP, or deoxyuridine monophosphate, is a deoxyribonucleotide consisting of a deoxyribose sugar, the uracil base, and a single phosphate group. It functions principally as an intermediate in the biosynthesis of thymidylate, a required precursor for DNA replication and repair.

Cellular pools of dUMP arise primarily from the deamination of dCMP and from the hydrolysis of dUTP by dUTPase, a reaction that helps sanitize the nucleotide pool and prevents uracil incorporation into DNA. Thymidylate synthase catalyzes the methylation of dUMP to deoxythymidine monophosphate (dTMP) using 5,10-methylene-tetrahydrofolate as the one-carbon donor. dTMP is subsequently phosphorylated to dTDP and dTTP, which are required for DNA synthesis.

A key regulatory aspect is the balance between dUMP and dTMP. Inhibition of thymidylate synthase—most notably by chemotherapeutic agents such as 5-fluorouracil or raltitrexed—reduces dTMP production, elevates dUMP/dUTP pools, and can lead to uracil misincorporation into DNA and DNA damage.

In addition to cytosolic metabolism, dUMP participates in mitochondrial nucleotide pools, contributing to mitochondrial DNA maintenance, though the details of these pools can differ from those in the cytosol.

Because dUMP is not itself incorporated into DNA by DNA polymerases, it primarily serves as a transient precursor in the pathway toward thymidine nucleotides, rather than as a direct component of DNA.