Document Detail


Roles of DNA-dependent protein kinase and ATM in cell-cycle-dependent radiation sensitivity in human cells.
MedLine Citation:
PMID:  12065055     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: The roles of DNA-dependent protein kinase (DNA-PK) and ATM in the cell-cycle-dependent radiosensitivity in human cells were investigated.
METHODS AND MATERIALS: A DNA-PK activity-deficient human glioblastoma cell line M059J, ataxia telangiectasia cell lines AT3BISV and AT5BIVA, and control cell lines were used. Wortmannin inhibited DNA-PK and ATM activities. Cells were synchronized by hydroxyurea. Progression through the cell cycle was analysed by flow cytometry.
RESULTS: M059J exhibited hyper-radiosensitivity throughout the cell cycle, with extreme hyper-radiosensitivity in G to early S-phase compared with the control cell line M059K. AT3BISV and AT5BIVA exhibited hyper-radiosensitivity throughout the cell cycle but showed a similar pattern of cell-cycle-dependent radiosensitivity to that observed in LM217 or HeLa cells. In AT3BISV and AT5BIVA, radiosensitization by wortmannin was observed throughout the cell cycle and was most prominent in G1 to early S-phase. Wortmannin did not sensitize M059J to ionizing radiation in any cell-cycle phase. DNA-PK activities were not different throughout the cell cycle.
CONCLUSION: The results suggest that (1) non-homologous endjoining plays a dominant role in G1 to early S-phase and a minor role in late S to G2-phase in repairing DNA double-strand breaks, (2) the role of ATM in repairing double-strand breaks may be almost cell-cycle-independent and (3) the dominant role of non-homologous end-joining during G1 to early S-phase is not due to cell-cycle-dependent fluctuations in DNA-PK activity.
Authors:
M Yoshida; Y Hosoi; H Miyachi; N Ishii; Y Matsumoto; A Enomoto; K Nakagawa; S Yamada; N Suzuki; T Ono
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of radiation biology     Volume:  78     ISSN:  0955-3002     ISO Abbreviation:  Int. J. Radiat. Biol.     Publication Date:  2002 Jun 
Date Detail:
Created Date:  2002-06-14     Completed Date:  2002-07-18     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  8809243     Medline TA:  Int J Radiat Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  503-12     Citation Subset:  IM; S    
Affiliation:
Departments of Radiation Research and Radiology, Tohoku University School of Medicine, Sendai, Japan.
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MeSH Terms
Descriptor/Qualifier:
Androstadienes / pharmacology
Ataxia Telangiectasia / metabolism,  pathology,  radiotherapy
Cell Cycle / physiology,  radiation effects*
Cell Cycle Proteins
Cell Line
Cell Survival / radiation effects
DNA-Activated Protein Kinase
DNA-Binding Proteins*
G1 Phase / physiology,  radiation effects
HeLa Cells
Humans
Nuclear Proteins
Phosphorylation
Protein-Serine-Threonine Kinases / metabolism*
Radiation Tolerance / physiology*
S Phase / physiology,  radiation effects
Serine / chemistry
Tumor Cells, Cultured
Tumor Suppressor Protein p53 / chemistry,  metabolism,  radiation effects
Tumor Suppressor Proteins
Chemical
Reg. No./Substance:
0/Androstadienes; 0/Cell Cycle Proteins; 0/DNA-Binding Proteins; 0/Nuclear Proteins; 0/Tumor Suppressor Protein p53; 0/Tumor Suppressor Proteins; 19545-26-7/wortmannin; 56-45-1/Serine; EC 2.7.11.1/DNA-Activated Protein Kinase; EC 2.7.11.1/PRKDC protein, human; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/ataxia telangiectasia mutated protein

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