Figure 1.

Uracil accumulation in DNA

The top schematic shows the conversion of dUTP to dUMP by dUTPase. dTTP is synthesized from either dUMP via de novo thymidylate biosynthesis pathway or from thymidine via the salvage pathway. The bottom schematic represents the reactions during an elevated dUTP/dTTP and low dUTPase activity. High dUTP results in an elevated rate of uracil incorporation into DNA by DNA polymerase. Uracil is excised under action of BER. Excessive excision and repair of uracil leads to chromosomal fragmentation and cell death.