Mammalian Pyrimidine Biosynthesis: Fresh Insights into an Ancient Pathway

The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition

“…In addition to proteins, cell growth is associated with the upregulation of de novo pyrimidine biosynthesis to meet the increased demand in nucleotides (Evans and Guy, 2004). Pyrimidine nucleotides serve as essential precursors for the synthesis of RNA and DNA, phospholipids, UDP-sugars and glycogen.…”

“…Pyrimidine nucleotides serve as essential precursors for the synthesis of RNA and DNA, phospholipids, UDP-sugars and glycogen. The ratelimiting step in the pyrimidine pathway is catalysed by the carbamoyl-phosphate synthetase (CPSase) enzyme, which is part of the large multifunctional protein CAD (Evans and Guy, 2004). Mitogenic stimulation of cells induces the phosphorylation of CAD and allosterically activates the CPSase domain by an MEK1/2-dependent mechanism (Graves et al, 2000).…”

Regulation of MAP Kinases by the VHR Dual-Specific Phosphatase – Implications for Cell Growth and Differentiation

“…35 ERKs also phosphorylate and activate several keys enzymes in nucleotide and DNA synthesis, like the carbamoyl-phosphate synthetase and the aspartate transcarbamylase. 36 The finding that the MSK1 kinase is a substrate for ERK also suggests a role of these kinases in G 2 phase regulation. 37 MSK1 phosphorylates histone H3 on residues important for chromosome condensation.…”

Pyrimidine pool imbalance induced by BLM helicase deficiency contributes to genetic instability in Bloom syndrome

“…Indeed, nucleotide pool imbalance, particularly for the pyrimidine pools, is known to result in genetic instability and oncogenic transformation 10,11 . Pyrimidine biosynthesis occurs through the de novo pathway, in which nucleotides are synthesized from small metabolites, or the salvage pathway, which recycles nucleosides and nucleotides 12 .…”