Document Detail

Bypass of senescence after disruption of p21CIP1/WAF1 gene in normal diploid human fibroblasts.
MedLine Citation:
PMID:  9242615     Owner:  NLM     Status:  MEDLINE    
Most somatic cells die after a finite number of cell divisions, a phenomenon described as senescence. The p21(CIP1/WAF1) gene encodes an inhibitor of cyclin-dependent kinases. Inactivation of p21 by two sequential rounds of targeted homologous recombination was sufficient to bypass senescence in normal diploid human fibroblasts. At the checkpoint between the prereplicative phase of growth and the phase of chromosome replication, cells lacking p21 failed to arrest the cell cycle in response to DNA damage, but their apoptotic response and genomic stability were unaltered. These results establish the feasibility of using gene targeting for genetic studies of normal human cells.
J P Brown; W Wei; J M Sedivy
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  277     ISSN:  0036-8075     ISO Abbreviation:  Science     Publication Date:  1997 Aug 
Date Detail:
Created Date:  1997-08-26     Completed Date:  1997-08-26     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  831-4     Citation Subset:  IM    
Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02912, USA.
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MeSH Terms
Aspartate Carbamoyltransferase / genetics
Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / genetics
Cell Aging / genetics*
Cell Division
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p21
Cyclins / genetics*,  physiology
DNA Damage
Dihydroorotase / genetics
G1 Phase
Gene Deletion*
Gene Targeting
Genetic Vectors
Multienzyme Complexes / genetics
Telomere / physiology
Grant Support
Reg. No./Substance:
0/CAD trifunctional enzyme; 0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Multienzyme Complexes; EC Carbamoyltransferase; EC; EC Synthase (Glutamine-Hydrolyzing)

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