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.
Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Rafal
R
Falinski
Margaret
M
Nieborowska-Skorska
Tomasz
T
Skorski
D000107:Acetylation; D000818:Animals; D002478:Cells, Cultured; D042002:Chromatin Assembly and Disassembly; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D006412:Hematopoietic Stem Cells; D051548:Histone Acetyltransferases / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016685:Mitomycin / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
D006657:Histones; D017382:Reactive Oxygen Species; D016685:Mitomycin; D051548:Histone Acetyltransferases; D016044:Fusion Proteins, bcr-abl; D006655:Histone Deacetylases