利用高时间分辨率显微镜分析活体细胞中的端粒快速运动。
Rapid telomere motions in live human cells analyzed by highly time-resolved microscopy.
机构信息
Department of Biochemistry and Biophysics, University of California at San Francisco, California, USA.
出版信息
Epigenetics Chromatin. 2008 Oct 27;1(1):4. doi: 10.1186/1756-8935-1-4.
BACKGROUND
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.
RESULTS
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.
CONCLUSION
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.
背景
端粒覆盖染色体末端并保护基因组。我们研究了活的人类癌细胞中的个体端粒。通过使用定量成像技术捕捉端粒运动，每秒钟获取完整的高分辨率三维数据集 200 秒，系统地分析了端粒动力学。
结果
同一癌细胞核内的个体端粒的运动广泛存在异质性。分析的一类染色体内部异染色质区域运动更均匀，运动和异质性比端粒少。在癌细胞中的单个端粒分析表明，较短的端粒表现出更多的运动，而更快的端粒运动是能量依赖的。实验性地增加端粒的整体长度会抑制端粒运动。相比之下，端粒去帽，而不是 DNA 损伤剂甲磺酸甲酯，显著增加了端粒运动。
结论
用于秒级、四维、活细胞显微镜成像和数据分析的新方法，允许在活细胞中系统地跟踪个体端粒，定义了人类细胞中端粒行为的一种以前未描述的形式，其中端粒运动的程度取决于端粒的长度和功能。
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