A missense mutation in the suc22 gene encoding the small subunit of ribonucleotide reductase significantly sensitizes fission yeast to chronic treatment with hydroxyurea.

Abstract

Ribonucleotide reductase (RNR) is essential for the biosynthesis of dNTPs and a therapeutic target. We have identified a missense mutation in suc22 , which encodes the small subunit of RNR in fission yeast. The suc22-S239F mutation significantly sensitizes the cells to chronic but not acute treatment with the RNR inhibitor hydroxyurea. Preliminary data indicate that the drug sensitivity is likely due to decreased RNR activity. Since S239F is the first missense mutation reported for suc22 and the mutated residue is highly conserved, the results will be useful for future yeast genetic studies and potentially, the development of new therapeutics targeting RNR.