Studies on novel DNA signatures of telomerase-independent telomere maintenance in Caenorhabditis elegans

Abstract

Telomeres at linear chromosomal ends cannot be replicated by DNA polymerase. This is called the end replication problem. If this problem is not solved, chromosomes will gradually be shortened along cell divisions. In order to maintain chromosome integrity through generations, organisms have invented telomere maintenance mechanisms. A specialized reverse transcriptase, telomerase, has evolved in ancient eukaryotic cells. Interestingly, telomerase has been lost a few times during evolution. In this situation, telomerase-independent mechanisms were adopted. Among telomerase-independent mechanisms, alternative lengthening of telomeres (ALT) has been studied in cancer formation. However, many studies on ALT did not have organismal perspectives. Here, I establish a model for organismal telomere maintenance after telomerase loss. Using Caenorhabditis elegans telomerase mutant, I have generated telomerase-independent survivors. These survivors mobilized specific internal sequence blocks for telomere lengthening, which we named TALTs (Templates for ALT). These TALTs region consist of a block of genomic DNA flanked by telomere-like sequences. Telomerase-independent survivors trans-duplicate TALTs, which is already cis-duplicated to chromosome ends, across the telomeres of all chromosomes. The switch from the telomerase-mediated to the TALT-mediated telomere maintenance mechanism shows a snapshot of telomere evolution. In addition, the molecular event of the cis-duplication of TALTs suggests a novel mechanism for subtelomere formation