Impact of p210(Bcr-Abl) on ultraviolet C wavelength-induced DNA damage and repair

Recently, it was shown that both Bcr and Bcr-Abl can interact with xeroderma pigmentosum group B (XPB/ERCC3), a protein implicated in DNA repair after UV-induced damage. To further analyze the effect of Bcr-Abl on the DNA damage response, we used cell lines stably transfected with the BCR-ABL gene a...

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Bibliographic Details
Published in:Clinical cancer research 2003-09, Vol.9 (10 Pt 1), p.3722
Main Authors: Laurent, Eunice, Mitchell, David L, Estrov, Zeev, Lowery, Megan, Tucker, Susan L, Talpaz, Moshe, Kurzrock, Razelle
Format: Article
Language:English
Subjects:
Annexin A5 - pharmacology
Apoptosis
Cell Line
Comet Assay
Dimerization
DNA Damage - drug effects
DNA Repair - drug effects
Enzyme Inhibitors - pharmacology
Fluorescein-5-isothiocyanate - pharmacology
Fusion Proteins, bcr-abl - genetics
Fusion Proteins, bcr-abl - therapeutic use
Genetic Vectors
Humans
Pyrimidine Dimers - chemistry
Radioimmunoassay
Time Factors
Transfection
Ultraviolet Rays
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Summary:Recently, it was shown that both Bcr and Bcr-Abl can interact with xeroderma pigmentosum group B (XPB/ERCC3), a protein implicated in DNA repair after UV-induced damage. To further analyze the effect of Bcr-Abl on the DNA damage response, we used cell lines stably transfected with the BCR-ABL gene and their parental counterparts (MBA-1 versus MO7E and Bcr-AblT1 versus 4A2(+)-pZAP) and several assays reflecting DNA repair: the comet assay, a radioimmunoassay for cyclobutane pyrimidine dimers, and clonogenic assays. After exposure to UVC (0.5-5.0 joules m(-2)), the Comet assay demonstrated greater efficiency of DNA repair in the BCR-ABL-positive cells (both MBA-1 and Bcr-AblT1) when compared with their parental counterparts. Furthermore, there was less production of the UV-induced DNA adduct-cyclobutane pyrimidine dimers-as well as a more rapid rate of disappearance of these adducts and greater UV survival (clonogenic assays) in MBA-1 cells as compared with MO7E cells. Apoptosis (annexin V-FITC/propidium iodide staining) was markedly reduced in the BCR-ABL-positive cells. These results indicate that BCR-ABL confers enhanced resistance to UV radiation-induced damage and increased efficiency of DNA repair and that these changes are associated with a protective antiapoptotic effect.
ISSN:1078-0432