De novo biosynthesis of pyrimidine deoxyribonucleotides (WP36)

Deoxyribonucleoside triphosphates (dNTPs) are the monomeric building blocks of DNA. In all cellular organisms, synthesis of the four canonical dNTPs (dATP, dGTP, dCTP, dTTP) required for DNA replication and repair involves the action of ribonucleotide reductase, which converts ribonucleotides to their corresponding deoxy- forms by substituting their 2-hydroxyl group with a hydrogen atom. S. cerevisiae contains a class Ia RNR that is composed of two large and two small subunits. RNR2 and RNR4 encode the small subunits, while the large subunits are encoded by either RNR1 (major isoform) or RNR3 (minor isoform). Budding yeast RNR accepts ribonucleoside diphosphates (e.g. ADP, UDP) as substrate and converts them to their corresponding deoxy- forms (e.g. dADP, dUDP). These dNDPs can then be phosphorylated by NDP kinase (Ynk1p) to yield dNTPs. In contrast to the class I RNRs in yeast and other eukaryotes, class II and class III RNRs found in archaea and many bacteria can produce dNTPs directly by using NTPs as substrates. Source: https://pathway.yeastgenome.org/

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