Linked Life Data

10585489

Source:http://linkedlifedata.com/resource/pubmed/id/10585489

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
50
pubmed:dateCreated
2000-1-13
pubmed:abstractText
Ribonucleotide reductase synthesizes dNDPs, a specific and limiting step in DNA synthesis, and can participate in neoplastic transformation when overexpressed. The small subunit (ribonucleotide reductase 2 (RNR2)) was cloned as a major product in a subtraction library from eukaryotic initiation factor 4E (eIF4E)-transformed cells (Chinese hamster ovary-4E (CHO-4E)). CHO-4E cells have 20-40-fold elevated RNR2 protein, reflecting an increased distribution of RNR2 mRNA to the heavy polysomes. CHO-4E cells display an altered cell cycle with shortened S phase, similar to cells selected for RNR2 overexpression with hydroxyurea. The function of ribonucleotide reductase as a checkpoint component of S progression was studied in yeast in which elevated eIF4E rescued S-arrested rnr2-68(ts) cells, by increasing recruitment of its mRNA to polysomes. Crosses between rnr2-68(ts) and mutant eIF4E (cdc33-1(ts)) engendered conditional synthetic lethality, with extreme sensitivity to hydroxyurea and the microtubule depolymerizing agent, benomyl. The double mutant (cdc33-1 rnr2-68) also identified a unique terminal phenotype, arrested with small bud and a randomly distributed single nucleus, which is distinct from those of both parental single mutants. This phenotype defines eIF4E and RNR2 as determinants in an important cell cycle checkpoint, in early/mid-S phase. These results also provide a link between protein and DNA synthesis and provide an explanation for cell cycle alterations induced by elevated eIF4E.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35991-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10585489-Animals, pubmed-meshheading:10585489-Benomyl, pubmed-meshheading:10585489-CHO Cells, pubmed-meshheading:10585489-Cell Cycle, pubmed-meshheading:10585489-Cloning, Molecular, pubmed-meshheading:10585489-Cricetinae, pubmed-meshheading:10585489-DNA Replication, pubmed-meshheading:10585489-Eukaryotic Initiation Factor-4E, pubmed-meshheading:10585489-Fibroblast Growth Factors, pubmed-meshheading:10585489-Gene Expression Regulation, pubmed-meshheading:10585489-Hydroxyurea, pubmed-meshheading:10585489-Microtubules, pubmed-meshheading:10585489-Ornithine Decarboxylase, pubmed-meshheading:10585489-Peptide Initiation Factors, pubmed-meshheading:10585489-Polyribosomes, pubmed-meshheading:10585489-Protein Biosynthesis, pubmed-meshheading:10585489-RNA, Messenger, pubmed-meshheading:10585489-Recombinant Proteins, pubmed-meshheading:10585489-Ribonucleotide Reductases, pubmed-meshheading:10585489-S Phase, pubmed-meshheading:10585489-Saccharomyces cerevisiae, pubmed-meshheading:10585489-Transcription, Genetic, pubmed-meshheading:10585489-Transfection
pubmed:year
1999
pubmed:articleTitle
Translational regulation of ribonucleotide reductase by eukaryotic initiation factor 4E links protein synthesis to the control of DNA replication.
pubmed:affiliation
Department of Biochemistry, Louisiana State University Medical Center, Shreveport, Louisiana 71130-3932, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.