Role of human Ku86 in telomere length maintenance and telomere capping
Role of human Ku86 in telomere length maintenance and telomere capping
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DOI：
10.1158/0008-5472.can-04-1381
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发表时间：
2004-10-15
期刊：
影响因子：
11.2
通讯作者：
Blasco, MA
中科院分区：
文献类型：
--
作者：
Jaco, I;Muñoz, P;Blasco, MA
Ku86 在端粒中的作用已在多种生物体中得到广泛研究。然而，Ku86 在人类端粒中的作用尚不清楚，因为 Ku86 缺失对于人类细胞来说是致命的。在这里，我们使用小干扰 RNA 来降低人类细胞中 Ku86 蛋白的水平。在用 Ku86 特异性小干扰 RNA 转染后 72 小时，Ku86 蛋白的量实现了类似 50% 的减少。 Ku86 水平的降低导致细胞活力迅速丧失，其特征是细胞群中细胞凋亡增加和有丝分裂指数降低。重要的是，Ku86 敲低伴随着端粒序列的显着丢失和染色体畸变的增加，包括涉及端粒序列的染色单体型融合。这些发现证明了 Ku86 在调节人类细胞端粒长度和端粒加帽方面的作用，这反过来又可能影响癌症和衰老。
The role of Ku86 at telomeres has been extensively studied in various organisms; however, a role for Ku86 at human telomeres was unknown because Ku86 deletion is lethal for human cells. Here, we used small interference RNA to decrease Ku86 protein levels in human cells. An similar to50% reduction in the amount of Ku86 protein was achieved 72 hours after transfection with Ku86-specific small interference RNAs. This decrease in Ku86 levels resulted in a rapid loss of cell viability characterized by increased apoptosis and decreased mitotic index in the cell population. Importantly, Ku86 knockdown was concomitant with a significant loss of telomeric sequences and with increased chromosomal aberrations, including chromatid-type fusions involving telomeric sequences. These findings demonstrate a role for Ku86 in regulating telomere length and telomere capping in human cells, which, in turn, could impact on cancer and aging.