Cheung Iris, Schertzer Michael, Rose Ann, Lansdorp Peter M
Terry Fox Laboratory, BC Cancer Agency Avenue, Vancouver, BC, Canada V5Z 1L3.
Nucleic Acids Res. 2006 Jan 10;34(1):96-103. doi: 10.1093/nar/gkj417. Print 2006.
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.
端粒酶对于维持大多数真核生物的端粒长度至关重要。人们提出了端粒酶的其他功能，但分子机制仍不清楚。我们研究了携带trt-1端粒酶逆转录酶基因突变的秀丽隐杆线虫。突变动物的产卵量逐渐减少，通常在五代后无法繁殖。使用聚合酶链反应（PCR）分析来测量五号染色体左臂上单个端粒重复序列的长度，我们观察到trt-1突变体每代大约丢失125bp的端粒DNA。在后代中观察到涉及复杂重组反应的染色体融合。引人注目的是，trt-1突变动物中出现了高频率的端粒，其重复序列比平均水平少得多。在表现出与trt-1突变体非常相似的端粒逐渐丢失的mrt-2突变体中未观察到这种异常短端粒情况。我们推测，除了维持平均端粒长度外，端粒酶还需要预防或修复与典型的“末端复制”问题无关的散发性端粒截短。
