title: BCR/ABL modifies the kinetics and fidelity of DNA double-strand breaks repair in hematopoietic cells.
abstract: The oncogenic BCR/ABL tyrosine kinase facilitates the repair of DNA double-strand breaks (DSBs). We find that after gamma-irradiation BCR/ABL-positive leukemia cells accumulate more DSBs in comparison to normal cells. These lesions are efficiently repaired in a time-dependent fashion by BCR/ABL-stimulated non-homologous end-joining (NHEJ) followed by homologous recombination repair (HRR) mechanisms. However, mutations and large deletions were detected in HRR and NHEJ products, respectively, in BCR/ABL-positive leukemia cells. We propose that unfaithful repair of DSBs may contribute to genomic instability in the Philadelphia chromosome-positive leukemias.
authors.affiliation: Center for Biotechnology, College of Science and Technology, Temple University, Bio-Life Sciences Building, Room 419, 1900 N. 12th Street, Philadelphia, PA 19122, USA.
authors.forename: Artur
authors.initials: A
authors.lastname: Slupianek
authors.forename: Michal O
authors.initials: MO
authors.lastname: Nowicki
authors.forename: Mateusz
authors.initials: M
authors.lastname: Koptyra
authors.forename: Tomasz
authors.initials: T
authors.lastname: Skorski
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D004249:DNA Damage; D004252:DNA Mutational Analysis; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D016044:Fusion Proteins, bcr-abl / Q000737:chemistry*; D005720:Gamma Rays; D017353:Gene Deletion; D016313:Genes, abl / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D051562:Proto-Oncogene Proteins c-bcr / Q000235:genetics; D011995:Recombination, Genetic; D015203:Reproducibility of Results; D013997:Time Factors
chemical_list: D016044:Fusion Proteins, bcr-abl; D051562:Proto-Oncogene Proteins c-bcr