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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-6-13
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1791-2423
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
443-51
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Suppression of DNA-PKcs and Ku80 individually and in combination: Different effects of radiobiology in HeLa cells.
pubmed:affiliation
Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan Hubei 430030, PR China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't