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|Title:||Elevated expression of artemis in human fibroblast cells is associated with cellular radiosensitivity and increased apoptosis|
|Keywords:||Cellular radiosensitivity;Defective DNA repair;Artemis overexpression|
|Publisher:||Nature Publishing Group|
|Citation:||British Journal of Cancer, 107(9): 1506 - 1513, Oct 2012|
|Abstract:||Background: The objective of this study was to determine the molecular mechanism(s) responsible for cellular radiosensitivity in two human fibroblast cell lines 84BR and 175BR derived from two cancer patients. Methods: Clonogenic assays were performed following exposure to increasing doses of gamma radiation to confirm radiosensitivity. γ-H2AX foci assays were used to determine the efficiency of DNA double strand break (DSB) repair in cells. Quantitative-PCR (Q-PCR) established the expression levels of key DNA DSB repair proteins. Imaging flow cytometry using Annexin V-FITC was used to compare artemis expression and apoptosis in cells. Results: Clonogenic cellular hypersensitivity in the 84BR and 175BR cell lines was associated with a defect in DNA DSB repair measured by the γ-H2AX foci assay. Q-PCR analysis and imaging flow cytometry revealed a two-fold overexpression of the artemis DNA repair gene which was associated with an increased level of apoptosis in the cells before and after radiation exposure. Over-expression of normal artemis protein in a normal immortalised fibroblast cell line NB1-Tert resulted in increased radiosensitivity and apoptosis. Conclusion: We conclude elevated expression of artemis is associated with higher levels of DNA DSB, radiosensitivity and elevated apoptosis in two radio-hypersensitive cell lines. These data reveal a potentially novel mechanism responsible for radiosensitivity and show that increased artemis expression in cells can result in either radiation resistance or enhanced sensitivity.|
|Description:||Copyright @ 2012 Nature Publishing Group|
This article has been made available through the Brunel Open Access Publishing Fund.
|Appears in Collections:||Biological Sciences|
Community Health and Public Health
Brunel OA Publishing Fund
Dept of Life Sciences Research Papers
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