The Ahmed Lab
Telomeres, the ends of linear chromosomes, are usually composed of simple repetitive sequences. In most organisms, telomeres are maintained by an enzyme called telomerase, which adds repeats to the end of a chromosome. Studies in yeast have identified five genes that are required for telomere replication. We have identified a number of C. elegans mutants with defects in telomere replication by looking for mortal germline mutants, which become sterile when propagated for several generations (Figure 1). Surprisingly, at least 11 genes are required for telomerase to act at C. elegans telomeres, some of which have yeast homologs that do not affect telomere metabolism. Thus, the mechanism of telomere replication in C. elegans and perhaps in other multicellular eukaryotes may be significantly different from that of fungi. We are using a variety of approaches to study telomerase, telomere replication, and the consequences of telomere dysfunction in C. elegans.
Figure 1. a, DAPI-stained oocyte nuclei from some late generation mortal germline mutants reveal fewer than the expected 6 pairs of chromosomes, indicating that chromosome fusions have occurred. b, End-to-end chromosome fusions isolated from mrt-2. c, Telomere length shortens in the mrt-1 and mrt-2 telomere replication mutant