| Bypass of senescence after disruption of p21CIP1/WAF1 gene in normal diploid human fibroblasts. | |
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MedLine Citation:
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PMID: 9242615 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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J P Brown; W Wei; J M Sedivy |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Science (New York, N.Y.) Volume: 277 ISSN: 0036-8075 ISO Abbreviation: Science Publication Date: 1997 Aug |
Date Detail:
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Created Date: 1997-08-26 Completed Date: 1997-08-26 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0404511 Medline TA: Science Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 831-4 Citation Subset: IM |
Affiliation:
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Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02912, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis 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 Electroporation Fibroblasts G1 Phase Gene Deletion* Gene Targeting Genetic Vectors Humans Multienzyme Complexes / genetics Telomere / physiology |
| Grant Support | |
ID/Acronym/Agency:
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GM41690/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CAD trifunctional enzyme; 0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Multienzyme Complexes; EC 2.1.3.2/Aspartate Carbamoyltransferase; EC 3.5.2.3/Dihydroorotase; EC 6.3.5.5/Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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