Document Detail


Heterologous expression of the human cyclin-dependent kinase inhibitor p21Cip1 in the fission yeast, Schizosaccharomyces pombe reveals a role for PCNA in the chk1+ cell cycle checkpoint pathway.
MedLine Citation:
PMID:  8730105     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fission yeast cells expressing the human gene encoding the cyclin-dependent kinase inhibitor protein p21Cip1 were severely compromised for cell cycle progress. The degree of cell cycle inhibition was related to the level of p21Cip1 expression. Inhibited cells had a 2C DNA content and were judged by cytology and pulsed field gel electrophoresis to be in the G2 phase of the cell cycle. p21Cip1 accumulated in the nucleus and was associated with p34cdc2 and PCNA. Thus, p21Cip1 interacts with the same targets in fission yeast as in mammalian cells. Elimination of p34cdc2 binding by mutation within the cyclin-dependent kinase binding domain of p21Cip1 exaggerated the cell cycle delay phenotype. By contrast, elimination of PCNA binding by mutation within the PCNA-binding domain completely abolished the cell cycle inhibitory effects. Yeast cells expressing wild-type p21Cip1 and the mutant form that is unable to bind p34cdc2 showed enhanced sensitivity to UV. Cell cycle inhibition by p21Cip1 was largely abolished by deletion of the chk1+ gene that monitors radiation damage and was considerably enhanced in cells deleted for the rad3+ gene that monitors both DNA damage and the completion of DNA synthesis. Overexpression of PCNA also resulted in cell cycle arrest in G2 and this phenotype was also abolished by deletion of chk1+ and enhanced in cells deleted for rad3+. These results formally establish a link between PCNA and the products of the rad3+ and chk1+ checkpoint genes.
Authors:
S Tournier; D Leroy; F Goubin; B Ducommun; J S Hyams
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular biology of the cell     Volume:  7     ISSN:  1059-1524     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  1996 Apr 
Date Detail:
Created Date:  1996-10-17     Completed Date:  1996-10-17     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  651-62     Citation Subset:  IM    
Affiliation:
Department of Biology, University College London, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Base Sequence
CDC2 Protein Kinase / physiology
Cell Cycle / drug effects,  radiation effects
Cloning, Molecular
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinases / antagonists & inhibitors*
Cyclins / genetics,  pharmacology*
DNA Repair
Enzyme Inhibitors / pharmacology*
Flow Cytometry
G2 Phase / drug effects
Humans
Molecular Sequence Data
Proliferating Cell Nuclear Antigen / physiology*
Schizosaccharomyces / cytology*,  genetics
Ultraviolet Rays
Grant Support
ID/Acronym/Agency:
//Wellcome Trust
Chemical
Reg. No./Substance:
0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Enzyme Inhibitors; 0/Proliferating Cell Nuclear Antigen; EC 2.7.11.22/CDC2 Protein Kinase; EC 2.7.11.22/Cyclin-Dependent Kinases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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