BCR-ABL1 kinase facilitates localization of acetylated histones 3 and 4 on DNA double-strand breaks

BCR-ABL1 kinase-positive leukemia cells accumulate high numbers of DNA double-strand breaks (DSBs) induced by the reactive oxygen species (ROS) or cytotoxic agents. To repair these lesions and prevent apoptosis BCR-ABL1 kinase stimulates the efficiency of DSB repair in leukemia cells. Histone acetylation-dependent chromatin re-modeling plays a crucial role in this process. Here we report that leukemia cells expressing BCR-ABL1 kinase displayed an enhanced histone acetylase activity (HAT) and reduced histone deacetylase activity (HDAC), which was associated with abundant expression of acetylated histones 3 and 4 (Ac-H3 and Ac-H4, respectively). Moreover, Ac-H3 and Ac-H4 readily co-localized with the spontaneous and mitomycin C-induced DSBs in BCR-ABL1-positive leukemia cells suggesting that histone acetylation and chromatin re-modeling is important for efficient repair of numerous DSBs.