Long Telomeres are Preferentially Extended During Recombination-Mediated Telomere Maintenance

Most human somatic cells do not express telomerase. Consequently, with each cell division their telomeres progressively shorten until replicative senescence is induced. Approximately 15% of human cancers maintain their telomeres using telomerase-independent, recombination-based mechanisms collectively termed Alternative Lengthening of Telomeres (ALT). In the yeast Saccharomyces cerevisiae, ALT cells are referred to as “survivors”. One type of survivor (type II) resembles human ALT cells in that both are defined by the amplification of telomeric repeats. We analyzed recombination-mediated telomere extension events at individual telomeres in telomerase-negative yeast during type II survivor formation and find that long telomeres are preferentially extended. Furthermore, we find that senescent cells with long telomeres are more efficient at bypassing senescence via the type II pathway. We speculate that telomere length may be important in determining whether cancer cells utilize telomerase or ALT to bypass replicative senescence.