Document Detail

Thioredoxin is required for deoxyribonucleotide pool maintenance during S phase.
MedLine Citation:
PMID:  16574642     Owner:  NLM     Status:  MEDLINE    
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.
Ahmet Koc; Christopher K Mathews; Linda J Wheeler; Michael K Gross; Gary F Merrill
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2006-03-29
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  281     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-05-29     Completed Date:  2006-08-07     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  15058-63     Citation Subset:  IM    
Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97331, USA.
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MeSH Terms
Cell Cycle Proteins / genetics,  metabolism
Deoxyribonucleotides / metabolism*
GTP-Binding Proteins / genetics,  metabolism
Gene Deletion
Genes, Fungal
Membrane Proteins / genetics,  metabolism
Ribonucleotide Reductases / metabolism
S Phase / physiology*
Saccharomyces cerevisiae / cytology*,  genetics,  metabolism*
Saccharomyces cerevisiae Proteins / genetics,  metabolism
Thioredoxins / genetics,  metabolism*
Grant Support
Reg. No./Substance:
0/CDC15 protein; 0/Cell Cycle Proteins; 0/Deoxyribonucleotides; 0/Membrane Proteins; 0/Saccharomyces cerevisiae Proteins; 0/TRX1 protein, S cerevisiae; 0/TRX2 protein, S cerevisiae; 52500-60-4/Thioredoxins; EC; EC 1.17.4.-/Ribonucleotide Reductases; EC 3.6.1.-/GTP-Binding Proteins

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