Document Detail

The Schizosaccharomyces pombe replication inhibitor Spd1 regulates ribonucleotide reductase activity and dNTPs by binding to the large Cdc22 subunit.
MedLine Citation:
PMID:  16317005     Owner:  NLM     Status:  MEDLINE    
Ribonucleotide reductase (RNR) is an essential enzyme that provides the cell with a balanced supply of deoxyribonucleoside triphosphates for DNA replication and repair. Mutations that affect the regulation of RNR in yeast and mammalian cells can lead to genetic abnormalities and cell death. We have expressed and purified the components of the RNR system in fission yeast, the large subunit Cdc22p, the small subunit Suc22p, and the replication inhibitor Spd1p. It was proposed (Liu, C., Powell, K. A., Mundt, K., Wu, L., Carr, A. M., and Caspari, T. (2003) Genes Dev. 17, 1130-1140) that Spd1 is an RNR inhibitor, acting by anchoring the Suc22p inside the nucleus during G1 phase. Using in vitro assays with highly purified proteins we have demonstrated that Spd1 indeed is a very efficient inhibitor of fission yeast RNR, but acting on Cdc22p. Furthermore, biosensor technique showed that Spd1p binds to the Cdc22p with a KD of 2.4 microM, whereas the affinity to Suc22p is negligible. Therefore, Spd1p inhibits fission yeast RNR activity by interacting with the Cdc22p. Similar to the situation in budding yeast, logarithmically growing fission yeast increases the dNTP pools 2-fold after 3 h of incubation in the UV mimetic 4-nitroquinoline-N-oxide. This increase is smaller than the increase observed in budding yeast but of the same order as the dNTP pool increase when synchronous Schizosaccharomyces pombe cdc10 cells are going from G1 to S-phase.
Pelle Håkansson; Lina Dahl; Olga Chilkova; Vladimir Domkin; Lars Thelander
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-11-28
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  281     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2006-01-17     Completed Date:  2006-03-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1778-83     Citation Subset:  IM    
Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå, Sweden.
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MeSH Terms
Cell Cycle Proteins / genetics,  metabolism*,  physiology*
Cloning, Molecular
DNA Replication
Deoxyribonucleotides / metabolism*
Escherichia coli / genetics
G1 Phase
Protein Subunits / metabolism
Recombinant Proteins / isolation & purification,  metabolism
Ribonucleotide Reductases / antagonists & inhibitors,  genetics,  metabolism*
Schizosaccharomyces / cytology,  enzymology,  genetics*
Schizosaccharomyces pombe Proteins / genetics,  metabolism*,  physiology*
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Deoxyribonucleotides; 0/Protein Subunits; 0/Recombinant Proteins; 0/Schizosaccharomyces pombe Proteins; 0/Spd1 protein, S pombe; 0/cdc22 protein, S pombe; EC 1.17.4.-/Ribonucleotide Reductases; EC protein, S pombe

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