Telomere dynamics in a human cancer cell line

Telomere maintenance is thought to be essential for immortalization of huma n cancer cells to compensate for the loss of DNA from the ends of chromosom es and to prevent chromosome fusion. We have investigated telomere dynamics in the telomerase-positive squamous cell carcinoma cell line SCC-61 by mar king the ends of chromosomes with integrated plasmid sequences so that chan ges in the length of individual telomeres could be monitored. Despite havin g very short telomeres, SCC-61 has a relatively stable genome and few telom ere associations. The marked telomeres in different SCC-61 clones have simi lar mean lengths which show little change with increasing time in culture. Thus, each marked telomere is maintained at a specific length, which we ter m the equilibrium mean length (EML). The Gaussian distribution in the lengt h of the marked telomeres demonstrates that telomeres continuously fluctuat e in length. Consistent with this observation, the mean lengths of the mark ed telomere in subclones of these cell lines initially differ, but then gra dually return to the EML of the original clone with increasing time in cult ure. The analysis of a clone with two marked telomeres demonstrated that ch anges in telomere length can occur on each marked telomere independently or coordinately on both telomeres. These results suggest that the short telom eres in many tumor cell lines do not result from an inability to properly m aintain telomeres at a specific length. (C) 1999 Academic Press.