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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Position effect of human telomeric repeats on replication timing
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Position effect of human telomeric repeats on replication timing

机译：人类端粒重复序列对复制时机的位置影响

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摘要

Telomeres are distinct structures, composed of short, repeated sequences, at the ends of all eukaryotic chromosomes. Telomeres have been shown in yeast to induce late replication in S phase and to silence transcription of neighboring genes. To examine the possibility of similar effects in human chromosomes, we studied cells from a subject with a microdeletion of 130 kb at the end of onc copy of chromosome arm 22q, repaired by the addition of telomere repeats. Using fluorescence in situ hybridization of S phase nuclei, a distinct difference was found in the replication timing or the breakpoint region between the intact and truncated copies of chromosome 22. This difference was evident as a shift from middle to late replication time of the breakpoint region adjacent to the repaired telomere. This finding suggests that the human telomere sequence influences activation of adja- cent replication origin(s). The difference in replication timing between the two chromosomes was not associated with differ- ences in sensitivity to digestion by DNase I or with methylation of regions immediately adjacent to the breakpoint. Further- more, both alleles of arylsulfatase A, a gene located at a distance of approximately 54 kb from the breakpoint, were expressed. We conclude that as in yeast, the proximity of telomeric DNA may induce a positional effect that delays the replication of adjacent chromosomal regions in humans.
机译：端粒是独特的结构，由短的重复序列组成，位于所有真核染色体的末端。端粒在酵母中已显示出可诱导S期晚期复制并沉默邻近基因的转录。为了检查在人类染色体上类似作用的可能性，我们研究了来自受试者的细胞，该细胞在染色体臂22q的onc拷贝末端微缺失了130 kb，并通过添加端粒重复序列进行了修复。使用S期核的荧光原位杂交，发现完整的和截短的22号染色体拷贝之间的复制时间或断裂点区域存在明显差异，这种差异明显体现为断裂点区域从复制中期到复制后期的转变。邻近修复的端粒。这一发现表明，人类端粒序列影响相邻复制起点的激活。两个染色体之间复制时间的差异与DNase I消化敏感性的差异或与断裂点紧邻的区域的甲基化无关。此外，还表达了芳基硫酸酯酶A的两个等位基因，这是一个距断点约54 kb的基因。我们得出的结论是，就像在酵母中一样，端粒DNA的接近可能会诱导位置效应，从而延迟人类中相邻染色体区域的复制。

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