NDLI: A Rare Combination of Ribonucleotide Reductases in the Social Amoeba Dictyostelium $discoideum^{*}$

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A Rare Combination of Ribonucleotide Reductases in the Social Amoeba Dictyostelium $discoideum^{*}$

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A Rare Combination of Ribonucleotide Reductases in the Social Amoeba Dictyostelium $discoideum^{*}$

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Klose, Ralph Söderbom, Fredrik Sahlin, Margareta Crona, Mikael Avesson, Lotta Sjöberg, Britt-marie Hinas, Andrea Lundin, Daniel
Description	Author Affiliation: Crona M ( Department of Molecular Biology and Functional Genomics, Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-10691 Stockholm, Sweden.)
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 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 $B_{12}$ 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.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	12
Volume Number	288
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2013-03-22
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Dictyostelium Enzymology Protozoan Proteins Metabolism Ribonucleotide Reductases Allosteric Regulation Coordination Complexes Chemistry Cytidine Diphosphate Genetics Physiology Enzyme Inhibitors Pharmacology Free Radicals Gene Expression Gene Expression Regulation, Enzymologic Guanosine Diphosphate Kinetics Phylogeny Antagonists & Inhibitors Spectrophotometry, Ultraviolet Spores, Protozoan Tyrosine Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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