Document Detail

Effect of separase depletion on ionizing radiation-induced cell cycle checkpoints and survival in human lung cancer cell lines.
MedLine Citation:
PMID:  18616699     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: This study is to evaluate the effect of separase depletion on cell cycle progression of irradiated and non-irradiated cells through the G(2)/M phases and consecutive cell survival. MATERIALS AND METHODS: Separase was depleted with siRNA in two human non-small cell lung carcinoma (NSCLC) cell lines. Cell cycle progression, mitotic fraction, DNA repair, apoptotic and clonogenic cell death were determined. RESULTS: By depletion of endogenous separase with siRNA in NSCLCs, we showed that separase affects progression through the G(2) phase. In non-irradiated exponentially growing cells, separase depletion led to an increased G(2) accumulation from 17.2% to 29.1% in H460 and from 15.7% to 30.9% in A549 cells and a decrease in mitotic cells. Depletion of separase significantly (P < 0.01) increased the fraction of radiation-induced G(2) arrested cells 30-56 h after irradiation and led to decrease in the mitotic fraction. This was associated with increased double-strand break repair as measured by gamma-H2AX foci kinetics in H460 cells and to a lesser extent in A549 cells. In addition, a decrease in the expression of mitotic linked cell death after irradiation was found. CONCLUSIONS: These results indicate that separase has additional targets involved in regulation of G(2) to M progression after DNA damage. Prolonged G(2) phase arrest in the absence of separase has consequences on repair of damaged DNA and cell death.
A Sak; I Fegers; M Groneberg; M Stuschke
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-06-19
Journal Detail:
Title:  Cell proliferation     Volume:  41     ISSN:  1365-2184     ISO Abbreviation:  Cell Prolif.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-08-14     Completed Date:  2008-09-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9105195     Medline TA:  Cell Prolif     Country:  England    
Other Details:
Languages:  eng     Pagination:  660-70     Citation Subset:  IM    
Department of Radiotherapy, University Hospital Essen, Essen, Germany.
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MeSH Terms
Carcinoma, Non-Small-Cell Lung / genetics*
Cell Cycle / radiation effects*
Cell Cycle Proteins / genetics*
Cell Division
Cell Line, Tumor
Cell Survival / radiation effects*
DNA Repair
Endopeptidases / deficiency,  genetics*
G2 Phase
Lung Neoplasms / genetics*
RNA, Messenger / genetics
Radiation, Ionizing*
Reg. No./Substance:
0/Cell Cycle Proteins; 0/RNA, Messenger; EC 3.4.-/Endopeptidases; EC

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