Martens U M, Zijlmans J M, Poon S S, Dragowska W, Yui J, Chavez E A, Ward R K, Lansdorp P M
Terry Fox Laboratory for Hematology/Oncology, British Columbia Cancer Research Centre, Vancouver, Canada.
Nat Genet. 1998 Jan;18(1):76-80. doi: 10.1038/ng0198-018.
Human chromosomes terminate in a series of T2AG3 repeats, which, together with associated proteins, are essential for chromosome stability. In somatic cells, these sequences are known to be gradually lost through successive cells divisions; however, information about changes on specific chromosomes is not available. Individual telomeres could mediate important biological effects as was shown in yeast, in which loss of a single telomere results in cell-cycle arrest and chromosome loss. We now demonstrate by quantitative fluorescence in situ hybridization (Q-FISH; ref. 7) that the number of T2AG3 repeats on specific chromosome arms is very similar in different tissues from the same donor and varies only to some extent between donors. In all sixteen individuals studied, telomeres on chromosome 17p were shorter than the median telomere length--a finding confirmed by analysis of terminal restriction fragments from sorted chromosomes. These observations provide evidence of chromosome-specific factors regulating the number of T2AG3 repeats in individual telomeres and raise the possibility that the relatively short telomeres on chromosome 17p contribute to the frequent loss of 17p alleles in human cancers.
人类染色体末端是一系列T2AG3重复序列，这些序列与相关蛋白一起，对染色体稳定性至关重要。在体细胞中，已知这些序列会在连续的细胞分裂过程中逐渐丢失；然而，关于特定染色体上变化的信息尚无可用数据。正如在酵母中所显示的那样，单个端粒可能介导重要的生物学效应，在酵母中，单个端粒的丢失会导致细胞周期停滞和染色体丢失。我们现在通过定量荧光原位杂交（Q-FISH；参考文献7）证明，来自同一供体的不同组织中，特定染色体臂上T2AG3重复序列的数量非常相似，仅在供体之间有一定程度的差异。在所有研究的16个人中，17号染色体短臂上的端粒短于端粒长度中位数——这一发现通过对分选染色体的末端限制片段分析得到证实。这些观察结果提供了染色体特异性因子调节单个端粒中T2AG3重复序列数量的证据，并提出了17号染色体短臂上相对较短的端粒可能导致人类癌症中17号染色体短臂等位基因频繁丢失的可能性。
