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Telomerase resets the homeostatic telomere length and prevents telomere dysfunction in immortalized human cells.

The enzyme telomerase correlates with cellular immortalization, and has been shown to be associated with more than 85% of all human cancers. Introduction of the catalytic subunit of telomerase (hTERT) into normal human cells has been shown to lengthen telomeres and extend life span, while ectopic expression of hTERT in immortal and tumor-derived cells lengthens telomeres even in the presence of endogenous telomerase. Because introduced telomerase has been shown to prevent genomic instability in normal cells, we sought to determine its effects on telomere dynamics and chromosome stability in our immortal cell line. We followed the telomere lengthening of an SV40 T antigen fibroblast cell line (SW39) with overexpressed hTERT for more than a year in culture and found that telomeres continued to elongate before the overall length stabilized. Overexpression of hTERT resets the weighted stable telomere length from an average of 4.5 kb to a final average length of 12.5 kb. The levels of telomerase activity and e...