High incidence of rapid telomere loss in telomerase-deficient Caenorhabditis elegans.
Telomerase is essential to maintain telomere length in most eukaryotes. Other functions for telomerase have been proposed but molecular mechanisms remain unclear. We studied Caenorhabditis elegans with a mutation in the trt-1 telomerase reverse transcriptase gene. Mutant animals showed a progressive decrease in brood size and typically failed to reproduce after five generations. Using PCR analysis to measure the length of individual telomere repeat tracks on the left arm of chromosome V we observed that trt-1 mutants lost approximately 125bp of telomeric DNA per generation. Chromosome fusions involving complex recombination reactions were observed in late generations. Strikingly, trt-1 mutant animals displayed a high frequency of telomeres with many fewer repeats than average. Such outlying short telomeres were not observed in mrt-2 mutants displaying progressive telomere loss very similar to trt-1 mutants. We speculate that, apart from maintaining the average telomere length, telomerase is required to prevent or repair sporadic telomere truncations that are unrelated to the typical 'end-replication' problems.
Cheung
Iris
I
Terry Fox Laboratory, BC Cancer Agency Avenue, Vancouver, BC, Canada V5Z 1L3.
Schertzer
Michael
M
Rose
Ann
A
Lansdorp
Peter M
PM
D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D007700:Kinetics; D019098:Telomerase / Q000235:genetics / Q000502:physiology*; D016615:Telomere / Q000378:metabolism*
D004268:DNA-Binding Proteins; D019098:Telomerase