The three-dimensional organization of telomeres in the nucleus of mammalian cells
The three-dimensional organization of telomeres in the nucleus of mammalian cells
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DOI：
10.1186/1741-7007-2-12
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发表时间：
2004-01-01
期刊：
影响因子：
5.4
通讯作者：
Mai, Sabine
中科院分区：
文献类型：
--
作者：
Chuang, Tony Chih Yuan;Moshir, Sharareh;Mai, Sabine
背景：光学显微镜原位观察多个遗传标记及其与研究核内三维染色体组织的相关性在过去十年中得到了很大的发展。这些方法在癌症研究中很重要，因为癌症的特点是多种改变，影响基因表达的调节和基因组的稳定性。因此，分析正常细胞和癌细胞间期细胞核的3D基因组组织是很有必要的。结果：我们描述了一种新的方法来研究哺乳动物细胞核内所有端粒在细胞周期中的分布。它是基于3D端粒荧光原位杂交，然后进行定量分析，确定端粒在整个细胞周期中在细胞核中的分布。这种方法使我们能够第一次确定端粒的组织是细胞周期依赖的，端粒在G2期组装成端粒盘。结论：研究结果强调了一种非随机的、动态的三维核端粒组织及其对基因组稳定性的重要性。根据我们的发现，似乎有可能在单个间期核和组织中检查暗示基因组不稳定的端粒聚集体，而不需要检查中期。这种监测基因组不稳定性的新途径可能会对癌症生物学、遗传学、诊断创新和医学治疗反应监测产生潜在影响。
Background: The observation of multiple genetic markers in situ by optical microscopy and their relevance to the study of three-dimensional (3D) chromosomal organization in the nucleus have been greatly developed in the last decade. These methods are important in cancer research because cancer is characterized by multiple alterations that affect the modulation of gene expression and the stability of the genome. It is, therefore, essential to analyze the 3D genome organization of the interphase nucleus in both normal and cancer cells.Results: We describe a novel approach to study the distribution of all telomeres inside the nucleus of mammalian cells throughout the cell cycle. It is based on 3D telomere fluorescence in situ hybridization followed by quantitative analysis that determines the telomeres' distribution in the nucleus throughout the cell cycle. This method enables us to determine, for the first time, that telomere organization is cell-cycle dependent, with assembly of telomeres into a telomeric disk in the G2 phase. In tumor cells, the 3D telomere organization is distorted and aggregates are formed.Conclusions: The results emphasize a non-random and dynamic 3D nuclear telomeric organization and its importance to genomic stability. Based on our findings, it appears possible to examine telomeric aggregates suggestive of genomic instability in individual interphase nuclei and tissues without the need to examine metaphases. Such new avenues of monitoring genomic instability could potentially impact on cancer biology, genetics, diagnostic innovations and surveillance of treatment response in medicine.