Rapid telomere motions in live human cells analyzed by highly time-resolved microscopy.
Rapid telomere motions in live human cells analyzed by highly time-resolved microscopy.
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DOI：
10.1186/1756-8935-1-4
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发表时间：
2008-10-27
影响因子：
3.9
通讯作者：
Blackburn EH
中科院分区：
文献类型：
--
作者：
Wang X;Kam Z;Carlton PM;Xu L;Sedat JW;Blackburn EH
端粒覆盖染色体末端并保护基因组。我们研究了活人类癌细胞中的单个端粒。通过使用定量成像捕获端粒运动，在 200 秒内每秒获取完整的高分辨率三维数据集，对端粒动力学进行了系统分析。同一癌细胞核内各个端粒的运动性存在很大差异。所分析的一类染色体内部异染色质区域比端粒运动更均匀，并且表现出更少的运动和异质性。癌细胞中的单个端粒分析表明，较短的端粒显示出更多的运动，而更快的端粒运动是能量依赖性的。通过实验增加端粒长度可抑制端粒运动。相比之下，端粒脱帽显着增加了端粒运动，但DNA损伤剂甲磺酸甲酯却没有。用于秒级、四维、活细胞显微成像和数据分析的新方法，允许系统跟踪活细胞中的单个端粒，定义了人类细胞中以前未描述的端粒行为形式，其中端粒运动的程度取决于端粒长度和功能。
Telomeres cap chromosome ends and protect the genome. We studied individual telomeres in live human cancer cells. In capturing telomere motions using quantitative imaging to acquire complete high-resolution three-dimensional datasets every second for 200 seconds, telomere dynamics were systematically analyzed. The motility of individual telomeres within the same cancer cell nucleus was widely heterogeneous. One class of internal heterochromatic regions of chromosomes analyzed moved more uniformly and showed less motion and heterogeneity than telomeres. The single telomere analyses in cancer cells revealed that shorter telomeres showed more motion, and the more rapid telomere motions were energy dependent. Experimentally increasing bulk telomere length dampened telomere motion. In contrast, telomere uncapping, but not a DNA damaging agent, methyl methanesulfonate, significantly increased telomere motion. New methods for seconds-scale, four-dimensional, live cell microscopic imaging and data analysis, allowing systematic tracking of individual telomeres in live cells, have defined a previously undescribed form of telomere behavior in human cells, in which the degree of telomere motion was dependent upon telomere length and functionality.