Sammanfattning

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.

Publicerad i

Journal of Biological Chemistry
2013, Volym: 288, nummer: 12, sidor: 8198-8208
Utgivare: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

SLU författare

• Avesson, Lotta

  • Institutionen för molekylärbiologi, Sveriges lantbruksuniversitet
    

• Hinas, Andrea

  • Institutionen för molekylärbiologi, Sveriges lantbruksuniversitet
    

• Söderbom, Fredrik

  • Institutionen för molekylärbiologi, Sveriges lantbruksuniversitet
    

UKÄ forskningsämne

Mikrobiologi
Genetik


Publikationens identifierare

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

Permanent länk till denna sida (URI)

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