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 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.
D017304:Annexin A5 / Q000494:pharmacology; D017209:Apoptosis; D002460:Cell Line; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D019281:Dimerization; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016650:Fluorescein-5-isothiocyanate / Q000494:pharmacology; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000627:therapeutic use*; D005822:Genetic Vectors; D006801:Humans; D011740:Pyrimidine Dimers / Q000737:chemistry; D011863:Radioimmunoassay; D013997:Time Factors; D014162:Transfection; D014466:Ultraviolet Rays
D017304:Annexin A5; D004791:Enzyme Inhibitors; D011740:Pyrimidine Dimers; D016044:Fusion Proteins, bcr-abl; D016650:Fluorescein-5-isothiocyanate