| Uncoupling of S phase and mitosis induced by anticancer agents in cells lacking p21. | |
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MedLine Citation:
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PMID: 8649519 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Precise coordination of the S and M phases of the eukaryotic cell cycle is critical not only for normal cell division, but also for effective growth arrest under conditions of stress. When damaged, a cell must communicate signals to both the mitotic and DNA synthesis machineries so that a mitotic block is not followed by an extra S phase, or vice versa. The biochemical mechanisms regulating this coordination, termed checkpoints, have been identified in lower eukaryotes, but are largely unknown in mammalian cells. Here we show that p21 WAF1/CIP1, the prototype inhibitor of cyclin-dependent kinases (CDKs), is required for this coordination in human cells. In the absence of p21, DNA-damaged cells arrest in a G2-like state, but then undergo additional S phases without intervening normal mitoses. They thereby acquire grossly deformed, polyploid nuclei and subsequently die through apoptosis. Perhaps not by coincidence, the DNA-damaging agents that can cause S/M uncoupling are used in the clinic to kill cancer cells preferentially. |
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Authors:
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T Waldman; C Lengauer; K W Kinzler; B Vogelstein |
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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: Nature Volume: 381 ISSN: 0028-0836 ISO Abbreviation: Nature Publication Date: 1996 Jun |
Date Detail:
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Created Date: 1996-07-25 Completed Date: 1996-07-25 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0410462 Medline TA: Nature Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 713-6 Citation Subset: IM |
Affiliation:
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The Howard Hughes Medical Institute, Johns Hopkins Oncology Center, and Program in Human Genetics, Baltimore, Maryland 21231, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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pharmacology* Apoptosis Bisbenzimidazole Camptothecin / pharmacology Cyclin-Dependent Kinase Inhibitor p21 Cyclin-Dependent Kinases / antagonists & inhibitors* Cyclins / physiology* DNA Damage Doxorubicin / pharmacology Enzyme Inhibitors* Etoposide / pharmacology Fluorescent Dyes Gamma Rays Humans Mitosis / drug effects, physiology* S Phase / drug effects, physiology* Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Enzyme Inhibitors; 0/Fluorescent Dyes; 23214-92-8/Doxorubicin; 23491-44-3/Bisbenzimidazole; 33419-42-0/Etoposide; 7689-03-4/Camptothecin; EC 2.7.11.22/Cyclin-Dependent Kinases |
| Comments/Corrections | |
Comment In:
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Nature. 1997 Jan 9;385(6612):123-5
[PMID:
8990112
]
Nature. 1996 Jun 20;381(6584):643-4 [PMID: 8649505 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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