Document Detail

Ribonucleotide reductase--new twists in an old tale.
MedLine Citation:
PMID:  2696342     Owner:  NLM     Status:  MEDLINE    
Although they are proliferatively quiescent, the cells in the intact adult rat liver express the gene coding for the M1 subunit of ribonucleotide reductase. But since they do not need deoxyribonucleotides, they promptly inactivate the 88 to 90 kDa M1 products and degrade them into 40 kDa fragments. Partial hepatectomy signals the remaining cells to start proliferating. Two hours before the onset of DNA replication, around 16 to 18 hr after partial hepatectomy, the cells start accumulating a large pool of functional ribonucleotide reductase M2 subunits. Near the end of the G1 build-up the cells step up M1 gene expression, stop inactivating, and reduce the degradation of the M1 products. The accumulating functional 88 to 90 kDa M1 subunits, each with more than one catalytic site, couple with functional M2 subunits to produce active ribonucleotide reductase holoenzyme which accumulates in the outer nuclear membrane from which they supply deoxyribonucleotide precursors to intranuclear replication enzymes. At the end of the S phase, the cell reduces M1 gene expression and resumes degrading 88 to 90 kDa M1 subunits. At least some of the 40 kDa M1 fragments are still active and can form partially active "holoenzymes" when mixed with a standard preparation of functional M2 subunits. The M1 control mechanism appears not to operate in hepatoma cells and Ehrlich ascites tumor cells, both of which maintain a pool of undegraded 88 to 90 kDa M1 components.
J F Whitfield; M Sikorska; T Youdale; L Brewer; R Richards; P R Walker
Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Advances in enzyme regulation     Volume:  28     ISSN:  0065-2571     ISO Abbreviation:  Adv. Enzyme Regul.     Publication Date:  1989  
Date Detail:
Created Date:  1990-03-19     Completed Date:  1990-03-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0044263     Medline TA:  Adv Enzyme Regul     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  113-23     Citation Subset:  IM    
Biological Sciences Division, National Research Council of Canada, Ottawa.
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MeSH Terms
Cell Line
DNA Polymerase II / metabolism
Liver / enzymology*
Liver Regeneration
Macromolecular Substances
Ribonucleotide Reductases / biosynthesis,  metabolism*
Tumor Cells, Cultured / enzymology
Reg. No./Substance:
0/Macromolecular Substances; EC 1.17.4.-/Ribonucleotide Reductases; EC 2.7.7.-/DNA Polymerase II

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