BCR-ABL1 激酶促进乙酰化组蛋白 3 和 4 在 DNA 双链断裂处的定位。
BCR-ABL1 kinase facilitates localization of acetylated histones 3 and 4 on DNA double-strand breaks.
机构信息
Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, PA 19140, USA.
出版信息
Leuk Res. 2012 Feb;36(2):241-4. doi: 10.1016/j.leukres.2011.10.007. Epub 2011 Oct 28.
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.
BCR-ABL1 激酶阳性白血病细胞积累大量由活性氧（ROS）或细胞毒性剂诱导的 DNA 双链断裂（DSB）。为了修复这些损伤并防止细胞凋亡，BCR-ABL1 激酶刺激白血病细胞中 DSB 修复的效率。组蛋白乙酰化依赖性染色质重塑在这个过程中起着至关重要的作用。在这里，我们报告说，表达 BCR-ABL1 激酶的白血病细胞表现出增强的组蛋白乙酰转移酶活性（HAT）和降低的组蛋白去乙酰化酶活性（HDAC），这与乙酰化组蛋白 3 和 4（分别为 Ac-H3 和 Ac-H4）的大量表达有关。此外，Ac-H3 和 Ac-H4 与 BCR-ABL1 阳性白血病细胞中的自发和丝裂霉素 C 诱导的 DSB 容易共定位，表明组蛋白乙酰化和染色质重塑对于大量 DSB 的有效修复很重要。
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