Source:http://linkedlifedata.com/resource/pubmed/id/21573502
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2011-6-13
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pubmed:abstractText |
DNA-dependent protein kinase (DNA-PK), including Ku80, Ku70 and DNA-PK catalytic subunit (DNA-PKcs), is the key protein in non-homologous end-joining (NHEJ) after DNA double-strand breaks (DSBs) appear. In this study, small hairpin interfering RNAs (siRNAs) targeting Ku80 and DNA- PKcs were used both individually and in combination, to explore the effects of these DSB proteins on HeLa cell functional changes after X-ray irradiation. HeLa cells co-transfected with Ku80-siRNA and DNA-PKcs-siRNA were more radiosensitive than the ones transfected individually. HeLa in the absence of Ku80 and pretreated with LY294002, a chemically specific PI 3-kinase inhibitor, resulted in cells that were even more sensitive to X-rays than HeLa/Ku80-siRNA transfected with DNA- PKcs-siRNA. The cells inhibited by Ku80 either individually or in combination with DNA-PKcs showed cell accumulation in the G2/M phase 48 h post-irradiation, similarly to control cells. However, cells transfected with DNA-PKcs-siRNA or pretreated with LY294002 had a prolonged G2/M delay, suggesting the accumulation of significant un-repaired DNA damage following inhibition of DSB repair proteins. In conclusion, these data indicate that the role of Ku80 in DSB repair could be compensated by other DSB repair proteins; co-inhibition would be a suitable strategy to enhance the radiosensitivity of cancer cells.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-(4-morpholinyl)-8-phenyl-4H-1-benz...,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Chromones,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Activated Protein Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Ku autoantigen,
http://linkedlifedata.com/resource/pubmed/chemical/Morpholines,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1791-2423
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
39
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
443-51
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pubmed:meshHeading |
pubmed-meshheading:21573502-Antigens, Nuclear,
pubmed-meshheading:21573502-Cell Cycle,
pubmed-meshheading:21573502-Cell Line, Tumor,
pubmed-meshheading:21573502-Chromones,
pubmed-meshheading:21573502-DNA-Activated Protein Kinase,
pubmed-meshheading:21573502-DNA-Binding Proteins,
pubmed-meshheading:21573502-Enzyme Activation,
pubmed-meshheading:21573502-Enzyme Inhibitors,
pubmed-meshheading:21573502-Gene Silencing,
pubmed-meshheading:21573502-HeLa Cells,
pubmed-meshheading:21573502-Humans,
pubmed-meshheading:21573502-Morpholines,
pubmed-meshheading:21573502-Neoplasms,
pubmed-meshheading:21573502-RNA, Small Interfering,
pubmed-meshheading:21573502-Radiation Tolerance,
pubmed-meshheading:21573502-X-Rays
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pubmed:year |
2011
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pubmed:articleTitle |
Suppression of DNA-PKcs and Ku80 individually and in combination: Different effects of radiobiology in HeLa cells.
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pubmed:affiliation |
Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan Hubei 430030, PR China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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