Sprung C N, Sabatier L, Murnane J P
Radiation Oncology Research Laboratory, University of California at San Francisco, 1855 Folsom Street, MCB 200, San Francisco, California, 94103, USA.
Exp Cell Res. 1999 Feb 25;247(1):29-37. doi: 10.1006/excr.1998.4293.
Telomere maintenance is thought to be essential for immortalization of human cancer cells to compensate for the loss of DNA from the ends of chromosomes and to prevent chromosome fusion. We have investigated telomere dynamics in the telomerase-positive squamous cell carcinoma cell line SCC-61 by marking the ends of chromosomes with integrated plasmid sequences so that changes in the length of individual telomeres could be monitored. Despite having very short telomeres, SCC-61 has a relatively stable genome and few telomere associations. The marked telomeres in different SCC-61 clones have similar mean lengths which show little change with increasing time in culture. Thus, each marked telomere is maintained at a specific length, which we term the equilibrium mean length (EML). The Gaussian distribution in the length of the marked telomeres demonstrates that telomeres continuously fluctuate in length. Consistent with this observation, the mean lengths of the marked telomere in subclones of these cell lines initially differ, but then gradually return to the EML of the original clone with increasing time in culture. The analysis of a clone with two marked telomeres demonstrated that changes in telomere length can occur on each marked telomere independently or coordinately on both telomeres. These results suggest that the short telomeres in many tumor cell lines do not result from an inability to properly maintain telomeres at a specific length.
端粒维持被认为对于人类癌细胞永生化至关重要，以补偿染色体末端DNA的丢失并防止染色体融合。我们通过用整合的质粒序列标记染色体末端来研究端粒酶阳性鳞状细胞癌细胞系SCC-61中的端粒动态，从而能够监测单个端粒长度的变化。尽管SCC-61的端粒非常短，但其基因组相对稳定，端粒关联很少。不同SCC-61克隆中的标记端粒具有相似的平均长度，随着培养时间的增加变化很小。因此，每个标记端粒都维持在一个特定长度，我们称之为平衡平均长度（EML）。标记端粒长度的高斯分布表明端粒长度不断波动。与这一观察结果一致，这些细胞系亚克隆中标记端粒的平均长度最初不同，但随着培养时间的增加逐渐恢复到原始克隆的EML。对具有两个标记端粒的克隆的分析表明，端粒长度的变化可以在每个标记端粒上独立发生，也可以在两个端粒上协同发生。这些结果表明，许多肿瘤细胞系中的短端粒并非由于无法将端粒正确维持在特定长度所致。
