A second pathway to degrade pyrimidine nucleic acid precursors in eukaryotes

Gorm Andersen, Olof Bjornberg, Silvia Polakova, Yuriy Pynyaha, Anna Rasmussen, Kasper Møller, Anders Hofer, Thomas Moritz, Michael Sandrini, Anna-Maria Merico, Concetta Compagno, Hans-Erik Aikerlund, Zoran Gojkovic, Jure Piskur

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    Pyrimidine bases are the central precursors for RNA and DNA, and their intracellular pools are determined by de novo, salvage and catabolic pathways. In eukaryotes, degradation of uracil has been believed to proceed only via the reduction to dihydrouracil. Using a yeast model, Saccharomyces kluyveri, we show that during degradation, uracil is not reduced to dihydrouracil. Six loci, named URC1-6 (for uracil catabolism), are involved in the novel catabolic pathway. Four of them, URC3,5, URC6, and URC2 encode urea amidolyase, uracil phosphoribosyltransferase, and a putative transcription factor, respectively. The gene products of URC1 and URC4 are highly conserved proteins with so far unknown functions and they are present in a variety of prokaryotes and fungi. In bacteria and in some fungi, URC1 and URC4 are linked on the genome together with the gene for uracil phosphoribosyltransferase (URC6). Urc1p and Urc4p are therefore likely the core components of this novel biochemical pathway. A combination of genetic and analytical chemistry methods demonstrates that uridine monophosphate and urea are intermediates, and 3-hydroxypropionic acid, ammonia and carbon dioxide the final products of degradation. The URC pathway does not require the presence of an active respiratory chain and is therefore different from the oxidative and rut pathways described in prokaryotes, although the latter also gives 3-hydroxypropionic acid as the end product. The genes of the URC pathway are not homologous to any of the eukaryotic or prokaryotic genes involved in pyrimidine degradation described to date.
    Original languageEnglish
    JournalJournal of Molecular Biology
    Volume380
    Issue number4
    Pages (from-to)656-666
    ISSN0022-2836
    DOIs
    Publication statusPublished - 2008

    Keywords

    • metabolic pathways
    • urea
    • nucleic acid recursors
    • uracil degradation
    • 3-hydroxypropionic acid

    Cite this

    Andersen, G., Bjornberg, O., Polakova, S., Pynyaha, Y., Rasmussen, A., Møller, K., ... Piskur, J. (2008). A second pathway to degrade pyrimidine nucleic acid precursors in eukaryotes. Journal of Molecular Biology, 380(4), 656-666. https://doi.org/10.1016/j.jmb.2008.05.029
    Andersen, Gorm ; Bjornberg, Olof ; Polakova, Silvia ; Pynyaha, Yuriy ; Rasmussen, Anna ; Møller, Kasper ; Hofer, Anders ; Moritz, Thomas ; Sandrini, Michael ; Merico, Anna-Maria ; Compagno, Concetta ; Aikerlund, Hans-Erik ; Gojkovic, Zoran ; Piskur, Jure. / A second pathway to degrade pyrimidine nucleic acid precursors in eukaryotes. In: Journal of Molecular Biology. 2008 ; Vol. 380, No. 4. pp. 656-666.
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    abstract = "Pyrimidine bases are the central precursors for RNA and DNA, and their intracellular pools are determined by de novo, salvage and catabolic pathways. In eukaryotes, degradation of uracil has been believed to proceed only via the reduction to dihydrouracil. Using a yeast model, Saccharomyces kluyveri, we show that during degradation, uracil is not reduced to dihydrouracil. Six loci, named URC1-6 (for uracil catabolism), are involved in the novel catabolic pathway. Four of them, URC3,5, URC6, and URC2 encode urea amidolyase, uracil phosphoribosyltransferase, and a putative transcription factor, respectively. The gene products of URC1 and URC4 are highly conserved proteins with so far unknown functions and they are present in a variety of prokaryotes and fungi. In bacteria and in some fungi, URC1 and URC4 are linked on the genome together with the gene for uracil phosphoribosyltransferase (URC6). Urc1p and Urc4p are therefore likely the core components of this novel biochemical pathway. A combination of genetic and analytical chemistry methods demonstrates that uridine monophosphate and urea are intermediates, and 3-hydroxypropionic acid, ammonia and carbon dioxide the final products of degradation. The URC pathway does not require the presence of an active respiratory chain and is therefore different from the oxidative and rut pathways described in prokaryotes, although the latter also gives 3-hydroxypropionic acid as the end product. The genes of the URC pathway are not homologous to any of the eukaryotic or prokaryotic genes involved in pyrimidine degradation described to date.",
    keywords = "metabolic pathways, urea, nucleic acid recursors, uracil degradation, 3-hydroxypropionic acid",
    author = "Gorm Andersen and Olof Bjornberg and Silvia Polakova and Yuriy Pynyaha and Anna Rasmussen and Kasper M{\o}ller and Anders Hofer and Thomas Moritz and Michael Sandrini and Anna-Maria Merico and Concetta Compagno and Hans-Erik Aikerlund and Zoran Gojkovic and Jure Piskur",
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    Andersen, G, Bjornberg, O, Polakova, S, Pynyaha, Y, Rasmussen, A, Møller, K, Hofer, A, Moritz, T, Sandrini, M, Merico, A-M, Compagno, C, Aikerlund, H-E, Gojkovic, Z & Piskur, J 2008, 'A second pathway to degrade pyrimidine nucleic acid precursors in eukaryotes', Journal of Molecular Biology, vol. 380, no. 4, pp. 656-666. https://doi.org/10.1016/j.jmb.2008.05.029

    A second pathway to degrade pyrimidine nucleic acid precursors in eukaryotes. / Andersen, Gorm; Bjornberg, Olof; Polakova, Silvia; Pynyaha, Yuriy; Rasmussen, Anna; Møller, Kasper; Hofer, Anders; Moritz, Thomas; Sandrini, Michael; Merico, Anna-Maria; Compagno, Concetta; Aikerlund, Hans-Erik; Gojkovic, Zoran; Piskur, Jure.

    In: Journal of Molecular Biology, Vol. 380, No. 4, 2008, p. 656-666.

    Research output: Contribution to journalJournal articleResearchpeer-review

    TY - JOUR

    T1 - A second pathway to degrade pyrimidine nucleic acid precursors in eukaryotes

    AU - Andersen, Gorm

    AU - Bjornberg, Olof

    AU - Polakova, Silvia

    AU - Pynyaha, Yuriy

    AU - Rasmussen, Anna

    AU - Møller, Kasper

    AU - Hofer, Anders

    AU - Moritz, Thomas

    AU - Sandrini, Michael

    AU - Merico, Anna-Maria

    AU - Compagno, Concetta

    AU - Aikerlund, Hans-Erik

    AU - Gojkovic, Zoran

    AU - Piskur, Jure

    PY - 2008

    Y1 - 2008

    N2 - Pyrimidine bases are the central precursors for RNA and DNA, and their intracellular pools are determined by de novo, salvage and catabolic pathways. In eukaryotes, degradation of uracil has been believed to proceed only via the reduction to dihydrouracil. Using a yeast model, Saccharomyces kluyveri, we show that during degradation, uracil is not reduced to dihydrouracil. Six loci, named URC1-6 (for uracil catabolism), are involved in the novel catabolic pathway. Four of them, URC3,5, URC6, and URC2 encode urea amidolyase, uracil phosphoribosyltransferase, and a putative transcription factor, respectively. The gene products of URC1 and URC4 are highly conserved proteins with so far unknown functions and they are present in a variety of prokaryotes and fungi. In bacteria and in some fungi, URC1 and URC4 are linked on the genome together with the gene for uracil phosphoribosyltransferase (URC6). Urc1p and Urc4p are therefore likely the core components of this novel biochemical pathway. A combination of genetic and analytical chemistry methods demonstrates that uridine monophosphate and urea are intermediates, and 3-hydroxypropionic acid, ammonia and carbon dioxide the final products of degradation. The URC pathway does not require the presence of an active respiratory chain and is therefore different from the oxidative and rut pathways described in prokaryotes, although the latter also gives 3-hydroxypropionic acid as the end product. The genes of the URC pathway are not homologous to any of the eukaryotic or prokaryotic genes involved in pyrimidine degradation described to date.

    AB - Pyrimidine bases are the central precursors for RNA and DNA, and their intracellular pools are determined by de novo, salvage and catabolic pathways. In eukaryotes, degradation of uracil has been believed to proceed only via the reduction to dihydrouracil. Using a yeast model, Saccharomyces kluyveri, we show that during degradation, uracil is not reduced to dihydrouracil. Six loci, named URC1-6 (for uracil catabolism), are involved in the novel catabolic pathway. Four of them, URC3,5, URC6, and URC2 encode urea amidolyase, uracil phosphoribosyltransferase, and a putative transcription factor, respectively. The gene products of URC1 and URC4 are highly conserved proteins with so far unknown functions and they are present in a variety of prokaryotes and fungi. In bacteria and in some fungi, URC1 and URC4 are linked on the genome together with the gene for uracil phosphoribosyltransferase (URC6). Urc1p and Urc4p are therefore likely the core components of this novel biochemical pathway. A combination of genetic and analytical chemistry methods demonstrates that uridine monophosphate and urea are intermediates, and 3-hydroxypropionic acid, ammonia and carbon dioxide the final products of degradation. The URC pathway does not require the presence of an active respiratory chain and is therefore different from the oxidative and rut pathways described in prokaryotes, although the latter also gives 3-hydroxypropionic acid as the end product. The genes of the URC pathway are not homologous to any of the eukaryotic or prokaryotic genes involved in pyrimidine degradation described to date.

    KW - metabolic pathways

    KW - urea

    KW - nucleic acid recursors

    KW - uracil degradation

    KW - 3-hydroxypropionic acid

    U2 - 10.1016/j.jmb.2008.05.029

    DO - 10.1016/j.jmb.2008.05.029

    M3 - Journal article

    C2 - 18550080

    VL - 380

    SP - 656

    EP - 666

    JO - Journal of Molecular Biology

    JF - Journal of Molecular Biology

    SN - 0022-2836

    IS - 4

    ER -

    Andersen G, Bjornberg O, Polakova S, Pynyaha Y, Rasmussen A, Møller K et al. A second pathway to degrade pyrimidine nucleic acid precursors in eukaryotes. Journal of Molecular Biology. 2008;380(4):656-666. https://doi.org/10.1016/j.jmb.2008.05.029