IMMORTALIZED CELLS WITH NO DETECTABLE TELOMERASE ACTIVITY - A REVIEW

Immortalization of human cells in culture is usually associated with e xpression oi telomerase activity, In some cases, however, no telomeras e activity is detectable even though comparison of the terminal restri ction fragment (TRF) pattern before and after immortalization shows th at lengthening of telomeres has occurred. The extreme heterogeneity in telomere length and the differences in the dynamics of telomere maint enance in telomerase-negative cell lines compared to telomerase-positi ve cell lines indicate that these cells have utilized one or more alte rnative mechanisms for lengthening of telomeres (ALT). All telomerase- negative immortalized fell lines examined to date show evidence of ALT activity, consistent with the hypothesis that telomere maintenance ei ther by telomerase or by ALT is required for immortalization. The natu re of the ALT mechanism(s) is currently unknown, but studies of telome re dynamics in an ALT cell line containing a marker just proximal to t he telomeric sequences show gradual shortening of the telomere followe d by rapid elongation. This is consistent with a non-reciprocal recomb inational mechanism similar to that found in telomerase-defective muta nt yeast strains.