Document Detail


High levels of Cdc7 and Dbf4 proteins can arrest cell-cycle progression.
MedLine Citation:
PMID:  16325502     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cdc7-Dbf4 serine/threonine kinase is essential for initiation of DNA replication. It was previously found that overexpression of certain replication proteins such as Cdc6 and Cdt1 in fission yeast resulted in multiple rounds of DNA replication in the absence of mitosis. Since this phenomenon is dependent upon the presence of wild-type Cdc7/Hsk1, we hypothesized that high levels of Cdc7 and/or Dbf4 could also cause multiple rounds of DNA replication, or could facilitate entry into S phase. To test this hypothesis, we transiently overexpressed hamster Cdc7, Dbf4 or both in CHO cells. Direct observations of individual cells by fluorescence microscopy and flow cytometric analysis on cell populations suggest that overexpression of Cdc7 and/or Dbf4 does not result in multiple rounds of DNA replication or facilitating entry into S phase. In contrast, moderately increased levels of Dbf4, but not Cdc7, cause cell-cycle arrest in G2/M. This G2/M arrest coincides with hyperphosphorylation of Cdc2/Cdk1 at Tyr-15, raising the possibility that high levels of Dbf4 may activate a G2/M cell-cycle checkpoint. Further increase in Cdc7 and/or Dbf4 by 2-4 fold can arrest cells in G1 and significantly slow down S-phase progression for the cells already in S phase.
Authors:
Baoqing Guo; Julia Romero; Byung-Ju Kim; Hoyun Lee
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-10-26
Journal Detail:
Title:  European journal of cell biology     Volume:  84     ISSN:  0171-9335     ISO Abbreviation:  Eur. J. Cell Biol.     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2005-12-05     Completed Date:  2006-03-02     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7906240     Medline TA:  Eur J Cell Biol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  927-38     Citation Subset:  IM    
Affiliation:
Department of Research, Northeastern Ontario Regional Cancer Centre, Sudbury, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
CHO Cells
Cell Cycle / physiology*
Cell Cycle Proteins / genetics,  metabolism*
Cricetinae
Cricetulus
DNA / genetics
DNA Replication
Female
Flow Cytometry
Gene Expression
Microscopy, Fluorescence
Protein-Serine-Threonine Kinases / analysis,  genetics,  physiology
Proteins / genetics,  metabolism*
S Phase / physiology
Spectrometry, Fluorescence
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/DBF4 protein, Cricetulus griseus; 0/Proteins; 9007-49-2/DNA; EC 2.7.11.1/Protein-Serine-Threonine Kinases

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