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Research article - Peer-reviewed, 2013

A Rare Combination of Ribonucleotide Reductases in the Social Amoeba Dictyostelium discoideum

Crona, Mikael; Avesson, Lotta; Sahlin, Margareta; Lundin, Daniel; Hinas, Andrea; Klose, Ralph; Söderbom, Fredrik; Sjöberg, Britt-Marie

Abstract

Ribonucleotide reductases (RNRs) catalyze the only pathway for de novo synthesis of deoxyribonucleotides needed for DNA replication and repair. The vast majority of eukaryotes encodes only a class I RNR, but interestingly some eukaryotes, including the social amoeba Dictyostelium discoideum, encode both a class I and a class II RNR. The amino acid sequence of the D. discoideum class I RNR is similar to other eukaryotic RNRs, whereas that of its class IIRNRis most similar to the monomeric class II RNRs found in Lactobacillus spp. and a few other bacteria. Here we report the first study of RNRs in a eukaryotic organism that encodes class I and class II RNRs. Both classes of RNR genes were expressed in D. discoideum cells, although the class I transcripts were more abundant and strongly enriched during mid-development compared with the class II transcript. The quaternary structure, allosteric regulation, and properties of the diiron-oxo/radical cofactor of D. discoideum class I RNR are similar to those of the mammalian RNRs. Inhibition of D. discoideum class I RNR by hydroxyurea resulted in a 90% reduction in spore formation and decreased the germination viability of the surviving spores by 75%. Class II RNR could not compensate for class I inhibition during development, and an excess of vitamin B-12 coenzyme, which is essential for class II activity, did not improve spore formation. We suggest that class I is the principal RNR during D. discoideum development and growth and is important for spore formation, possibly by providing dNTPs for mitochondrial replication.

Published in

Journal of Biological Chemistry
2013, Volume: 288, number: 12, pages: 8198-8208
Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

      SLU Authors

    • Avesson, Lotta

      • Department of Molecular Biology, Swedish University of Agricultural Sciences
      • Hinas, Andrea

        • Department of Molecular Biology, Swedish University of Agricultural Sciences
        • Söderbom, Fredrik

          • Department of Molecular Biology, Swedish University of Agricultural Sciences

        UKÄ Subject classification

        Microbiology
        Genetics

        Publication identifier

        DOI: https://doi.org/10.1074/jbc.M112.442434

        Permanent link to this page (URI)

        https://res.slu.se/id/publ/43078