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A Rare Combination of Ribonucleotide Reductases in the Social Amoeba Dictyostelium discoideum
Arrhenius Laboratories for Natural Sciences.
Swedish University of Agricultural Sciences.
Arrhenius Laboratories for Natural Sciences ; Stockholm University.
Stockholm University. (Jarone Pinhassi)ORCID iD: 0000-0002-8779-6464
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2013 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 288, no 12, p. 8198-8208Article in journal (Refereed) Published
Abstract [en]

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 II RNR is 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 B12 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.

Place, publisher, year, edition, pages
2013. Vol. 288, no 12, p. 8198-8208
Keywords [en]
Development, Dictyostelium, Gene Expression, Phylogenetics, Ribonucleotide Reductase, 5′-Deoxyadenosylcobalamin, Hydroxyurea, Spore Formation
National Category
Biochemistry and Molecular Biology
Research subject
Chemistry, Biochemistry
Identifiers
URN: urn:nbn:se:lnu:diva-50953DOI: 10.1074/jbc.M112.442434OAI: oai:DiVA.org:lnu-50953DiVA, id: diva2:912981
Available from: 2016-03-18 Created: 2016-03-17 Last updated: 2017-11-30Bibliographically approved

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Lundin, Daniel

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