Thioredoxin is required for deoxyribonucleotide pool maintenance during S phase.

Thioredoxin was initially identified by its ability to serve as an electron donor for ribonucleotide reductase in vitro. Whether it serves a similar function in vivo is unclear. In Saccharomyces cerevisiae, it was previously shown that Deltatrx1 Deltatrx2 mutants lacking the two genes for cytosolic thioredoxin have a slower growth ...
rate because of a longer S phase, but the basis for S phase elongation was not identified. The hypothesis that S phase protraction was due to inefficient dNTP synthesis was investigated by measuring dNTP levels in asynchronous and synchronized wild-type and Deltatrx1 Deltatrx2 yeast. In contrast to wild-type cells, Deltatrx1 Deltatrx2 cells were unable to accumulate or maintain high levels of dNTPs when alpha-factor- or cdc15-arrested cells were allowed to reenter the cell cycle. At 80 min after release, when the fraction of cells in S phase was maximal, the dNTP pools in Deltatrx1 Deltatrx2 cells were 60% that of wild-type cells. The data suggest that, in the absence of thioredoxin, cells cannot support the high rate of dNTP synthesis required for efficient DNA synthesis during S phase. The results constitute in vivo evidence for thioredoxin being a physiologically relevant electron donor for ribonucleotide reductase during DNA precursor synthesis.
Mesh Terms:
Cell Cycle Proteins, Deoxyribonucleotides, GTP-Binding Proteins, Gene Deletion, Genes, Fungal, Kinetics, Membrane Proteins, Mutation, Peroxiredoxins, Ribonucleotide Reductases, S Phase, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Thioredoxins
J. Biol. Chem.
Date: Jun. 02, 2006
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