Studies on the Novel Mechanism of Telomere Maintenance in Caenorhabditis elegans

Abstract

When telomeres lose their ability to protect chromosome ends, cells enter crisis and can only escape death by acquiring the ability to maintain telomere length. The survivors of crisis are often tumorigenic and maintain telomere length commonly through the reactivation of telomerase, but occasionally activate an alternative mechanism called ALT (alternative lengthening of telomeres). Here, I established stably-maintained survivor lines of the nematode C. elegans that activate an ALT mechanism to escape from the sterility phenotype caused by telomerase deletion. ALT survivors utilized, depending on their genetic backgrounds, either one of two specific internal genomic regions as templates for telomere lengthening. Either one of these experimentally defined DNA fragments Template of ALT (TALT) element 1 and 2, each consisting of a block of genomic DNA flanked by telomere-like sequences had already been copied to a proximal telomere region of one chromosome before ALT occurred and was incorporated into most chromosome ends by ALT. The TALT elements that I identified in this study represent a novel mechanism of stabilizing linear chromosomes in the absence of telomerase. Our data have implications in cancer biology, as it is possible that at least some ALT tumors maintain telomeres through a TALT-like mechanism.