Recombination involving interstitial telomere repeat-like sequences promotes chromosomal instability in Chinese hamster cells
Recombination involving interstitial telomere repeat-like sequences promotes chromosomal instability in Chinese hamster cells
复制标题
DOI：
10.1093/carcin/19.2.259
复制
发表时间：
1998-02-01
期刊：
影响因子：
4.7
通讯作者：
Morgan, WF
中科院分区：
文献类型：
--
作者：
Day, JP;Limoli, CL;Morgan, WF
哺乳动物染色体的物理末端被端粒序列的串联重复序列（TTAGGG）（n）加帽。用标记的（TTAGGG）（n）探针进行荧光原位杂交后，端粒重复样序列在多种脊椎动物的染色体内不同位点上显示为离散的条带。越来越多的证据表明这些位点可能是染色体重排、脆性和肿瘤形成的热点。我们研究了在来自人仓鼠杂交细胞系的仓鼠染色体中发现的间质端粒带是否是DNA损伤剂诱导的染色体重排的热点，我们的数据表明，细胞在G1期暴露于X射线或限制性核酸内切酶后，在第一次有丝分裂时观察到的染色体重排中涉及到间质端粒带。频率比根据它们的大小预期的高五倍。此外，我们已经扩展了这些观察，首次证明这些间质性端粒重复样序列参与了在辐射后多代X射线暴露存活的细胞后代中观察到的延迟染色体不稳定性。在两个高度不稳定的克隆显示多个人口的重排染色体，间质端粒带观察到在网站之间的重组人类和仓鼠染色体的频率比预期高5至6倍。仓鼠染色体间质端粒带也有重排和扩增。这些重排发生在用DNA损伤剂处理后存活的细胞的克隆扩增期间，并表明间质端粒带在驱动染色体不稳定性中的作用。我们从观察到的数据中得出结论，间质端粒带作为重组热点发挥作用，参与产生多种染色体重排，这些重排可以立即观察到，也可以作为细胞暴露于DNA损伤剂的延迟效应观察到。
The physical termini of mammalian chromosomes are capped with tandem repeats of the telomere sequence (TTAGGG)(n). After fluorescence in situ hybridization with a labeled (TTAGGG)(n) probe, telomere-repeat-like sequences are seen as discrete bands at distinct intrachromosomal sites in a variety of vertebrate species. There is increasing evidence that these sites may be hot-spots for chromosomal rearrangements, fragility and neoplasia. We have investigated whether the interstitial telomere bands found in hamster chromosomes from a human hamster hybrid cell line are hot-spots for chromosome rearrangements induced by DNA-damaging agents, Our data indicate that the interstitial telomere bands are involved in chromosomal rearrangements observed at the first mitosis after G1 exposure of cells to X-rays or restriction endonucleases at a four- to fivefold higher frequency than expected based on their size. In addition, we have extended these observations to demonstrate for the first time that these interstitial telomere-repeat-like sequences participate in the delayed chromosomal instability observed in the progeny of cells surviving X-ray-exposure at multiple generations after irradiation. In two highly unstable clones showing multiple populations of rearranged chromosomes, interstitial telomere bands were observed at the site of recombination between the human and hamster chromosomes at a five- to sixfold higher frequency than expected. There were also rearrangement and amplification of the interstitial telomere bands within the hamster chromosomes. These rearrangements occur during clonal expansion of cells surviving treatment with DNA-damaging agents and suggest a role for the interstitial telomere band in driving chromosomal instability. We conclude from the observed data that interstitial telomere bands function as recombinational hot-spots that participate in generating the diverse chromosome rearrangements observed both immediately and as a delayed effect of cellular exposure to DNA damaging agents.