TELOMERE DYNAMICS IN AN IMMORTAL HUMAN CELL-LINE
TELOMERE DYNAMICS IN AN IMMORTAL HUMAN CELL-LINE
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DOI：
10.1002/j.1460-2075.1994.tb06822.x
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发表时间：
1994-10-17
期刊：
影响因子：
11.4
通讯作者：
MORGAN, WF
中科院分区：
文献类型：
--
作者：
MURNANE, JP;SABATIER, L;MORGAN, WF
整合转染质粒DNA在染色体13的端粒在一个永生化的猿猴病毒40转化的人类细胞系提供了第一次机会，研究多态性的端粒重复序列的数量在一个单一的染色体的末端。选择该细胞系的三个亚克隆进行分析：一个在13号染色体上具有长端粒，一个具有短端粒，一个具有这样的极端多态性，即没有明显的条带可辨别。进一步的亚克隆研究表明，端粒多态性既有渐变的，也有快速变化的，有时还涉及到多种酶的参与。这种逐渐的变化是由于端粒的缩短，其速率与没有端粒酶的体细胞端粒的报道相似，最终导致几乎所有端粒的丢失。然而，端粒一般不会完全丢失，如在亚端粒质粒序列中不存在多态性所示。相反，长度小于几百个碱基对的端粒显示出快速的、高度异质性的大小增加。端粒长度的快速变化也发生在较长的端粒上。这种类型的端粒长度变化的频率在亚克隆中各不相同，并与染色体融合相关。因此，端粒长度的快速变化偶尔会导致端粒重复序列的完全丢失。端粒长度的快速变化与酵母中的端粒丢失和染色体不稳定性有关，并且可能是在许多人类肿瘤细胞系中观察到的染色体融合率高的原因。
The integration of transfected plasmid DNA at the telomere of chromosome 13 in an immortalized simian virus 40-transformed human cell line provided the first opportunity to study polymorphism in the number of telomeric repeat sequences on the end of a single chromosome. Three subclones of this cell line were selected for analysis: one with a long telomere on chromosome 13, one with a short telomere, and one with such extreme polymorphism that no distinct band was discernible. Further subcloning demonstrated that telomere polymorphism resulted from both gradual changes and rapid changes that sometimes involved many kilobases. The gradual changes were due to the shortening of telomeres at a rate similar to that reported for telomeres of somatic cells without telomerase, eventually resulting in the loss of nearly all of the telomere. However, telomeres were not generally lost completely, as shown by the absence of polymorphism in the subtelomeric plasmid sequences. Instead, telomeres that were less than a few hundred base pairs in length showed a rapid, highly heterogeneous increase in size. Rapid changes in telomere length also occurred on longer telomeres. The frequency of this type of change in telomere length varied among the subclones and correlated with chromosome fusion. Therefore, the rapid changes in telomere length appeared occasionally to result in the complete loss of telomeric repeat sequences. Rapid changes in telomere length have been associated with telomere loss and chromosome instability in yeast and could be responsible for the high rate of chromosome fusion observed in many human tumor cell lines.