Short telomeres on human chromosome 17p
Short telomeres on human chromosome 17p
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DOI：
10.1038/ng0198-018
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发表时间：
1998-01-01
期刊：
影响因子：
30.8
通讯作者：
Lansdorp, PM
中科院分区：
文献类型：
--
作者：
Martens, UM;Zijlmans, JMJM;Lansdorp, PM
人类染色体终止于一系列T(2)AG(3)，重复(1)，与相关蛋白质一起，对染色体的稳定性至关重要(2，3)。在体细胞中，已知这些序列在连续的细胞分裂中逐渐丢失(4，5)；然而，关于特定染色体的变化的信息是不可用的。在酵母中，单个端粒可以调节重要的生物学效应，其中单个端粒的丢失会导致细胞周期停滞和染色体丢失[6]。我们现在通过定量荧光原位杂交(Q-FISH；Ref.7)在同一供体的不同组织中，T(2)AG(3)在特定染色体臂上的重复数目非常相似，只是在供体之间存在一定程度的差异。在所有16个被研究的个体中，染色体17p上的端粒都比端粒的中值长度短--这一发现得到了来自已排序染色体的末端限制性片段的分析的证实。这些观察结果提供了染色体特异性因素调节单个端粒中T(2)AG(3)重复数的证据，并提高了17p染色体上相对较短的端粒导致人类癌症中17p等位基因频繁丢失的可能性。
Human chromosomes terminate in a series of T(2)AG(3), repeats(1), which, together with associated proteins, are essential for chromosome stability(2,3). In somatic cells, these sequences are known to be gradually lost through successive cells divisions(4,5); 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(6). We now demonstrate by quantitative fluorescence in situ hybridization (Q-FISH; ref. 7) that the number of T(2)AG(3) 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 T(2)AG(3) 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.