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Pathway: de novo biosynthesis of pyrimidine deoxyribonucleotides

Biochemical pathways in S. cerevisiae are manually curated and maintained in the YeastPathways database. This page summarizes the genes, enzymes, and metabolites involved in the pathway, along with the curated literature.

Pathway Name
de novo biosynthesis of pyrimidine deoxyribonucleotides
Pathway ID
YEAST-DE-NOVO-PYRMID-DNT
SGD ID
SGD:S000249772
Genes
CDC21 | CDC8 | DUT1 | RNR1 | RNR2 | RNR3 | RNR4 | TRX1 | TRX2 | TRX3 | URA6 | YNK1
Aliases
deoxypyrimidine nucleotide/nucleoside metabolism
Chemical Compounds
2'-deoxycytosine 5'-monophosphate(2-) | ADP(3-) | ATP(4-) | CDP(3-) | UDP(3-) | ammonium | dCDP(3-) | dCTP(4-) | dTDP(3-) | dTMP(2-) | dTTP(4-) | dUDP(3-) | dUMP(2-) | dUTP(4-) | diphosphoric acid | hydron | water

Pathway Diagram

Diagram of the pathway from YeastPathways. Click "View interactive diagram at YeastPathways" for the zoomable, clickable version.

de novo biosynthesis of pyrimidine deoxyribonucleotides pathway diagram

View interactive diagram at YeastPathways

Pathway Summary

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. In S. cerevisiae, the only dNDP that cannot be synthesized directly by RNR is dTDP. Synthesis of thymine-containing nucleotides requires dUMP, which can be formed via the removal of pyrophosphate from dUTP by dUTP pyrophosphatase (Dut1p). dTMP is synthesized from dUMP when the latter molecule receives a methyl group from 5,10-methylene-tetrahydrofolate via thymidylate synthase (Cdc21p). The subsequent phosphorylation of dTMP by thymidylate kinase (Cdc8p) yields dTDP, which can be phosphorylated once more by Ynk1p to yield the end product dTTP.

Genes Involved

Genes whose products participate in this pathway, with their systematic names, EC numbers (where the gene product is an enzyme with an assigned EC number), and the gene's SGD description.

GeneSystematic NameEC NumberDescription
CDC21 YOR074C 2.1.1.45 Thymidylate synthase
CDC8 YJR057W 2.7.4.9 Nucleoside monophosphate and nucleoside diphosphate kinase
DUT1 YBR252W 3.6.1.23 Deoxyuridine triphosphate diphosphatase (dUTPase)
RNR1 YER070W 1.17.4.1 Major isoform of large subunit of ribonucleotide-diphosphate reductase
RNR2 YJL026W 1.17.4.1 Ribonucleotide-diphosphate reductase (RNR), small subunit
RNR3 YIL066C 1.17.4.1 Minor isoform of large subunit of ribonucleotide-diphosphate reductase
RNR4 YGR180C 1.17.4.1 Ribonucleotide-diphosphate reductase (RNR) small subunit
TRX1 YLR043C Cytoplasmic thioredoxin isoenzyme
TRX2 YGR209C Cytoplasmic thioredoxin isoenzyme
TRX3 YCR083W Mitochondrial thioredoxin
URA6 YKL024C 2.7.4.14 Uridylate kinase
YNK1 YKL067W 2.7.4.6 Nucleoside diphosphate kinase

Functional Networks

Functional Networks show how the genes in this pathway work together: a graph linking the pathway to its genes and their shared GO biological-process terms and phenotype observables, and the GO-CAM causal activity models that involve these genes.

Shared Annotations

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GO-CAMs

GO-CAM (Gene Ontology Causal Activity Model) pathway models that involve the genes in this pathway. A gene can participate in more than one model, so use the dropdown to switch between them; the model for this pathway is shown by default.

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GO Enrichment

Gene Ontology biological-process terms enriched among the genes in this pathway, computed with GO Term Finder. Terms are shown with the number of pathway genes annotated to them and the corrected p-value.

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References

List of references used specifically to curate the information on this page.

Resources

YeastPathways