Normal human telomeres are not late replicating
Normal human telomeres are not late replicating
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DOI：
10.1006/excr.1999.4602
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发表时间：
1999-09-15
影响因子：
3.7
通讯作者：
Shay, JW
中科院分区：
文献类型：
--
作者：
Wright, WE;Tesmer, VM;Shay, JW
酵母中的端粒是晚期复制的。在酵母中，位于端粒附近的基因可以被抑制（端粒位置效应），导致端粒可能是异染色质的假设，并可能控制亚端粒基因的表达。此外，酵母端粒被加工成在S期结束时具有短暂的长突出端。通过确定正常人二倍体成纤维细胞中端粒复制和加工的时间来检查酵母数据对人类生物学的适用性。端粒纯化同步化细胞，已标记5-溴脱氧尿苷（BrdU）在每小时的时间间隔，标记的端粒的分数进行了分析，通过检索与抗BrdU抗体。我们确定，正常的人类端粒复制整个S期，而不是非常晚复制。此外，复制的总体时间不受年轻细胞与老年细胞或其端粒在转染端粒酶催化亚基后被拉长的细胞中端粒长度的影响。最后，在子端粒中的G-丰富的突出的长度的不对称性所产生的领先与落后的链合成被证明是建立在1小时内的端粒复制，这表明有没有显着的延迟之间的合成和处理事件，有助于建立不对称的突出。因此，人类端粒的复制和加工时间与酵母非常不同。(C)北京：科学出版社.
Telomeres in yeast are late replicating. Genes placed next to telomeres in yeast can be repressed (telomere positional effects), leading to the hypothesis that telomeres may be heterochromatic and may control the expression of subtelomeric genes. In addition, yeast telomeres are processed to have a transient long overhang at the end of S phase. The applicability of the yeast data to human biology was examined by determining the timing of telomere replication and processing in normal human diploid fibroblasts. Telomeres were purified from synchronized cells that had been labeled with 5-bromodeoxyuridine (BrdU) at hourly intervals, and the fraction of labeled telomeres was analyzed by retrieval with anti-BrdU antibodies. We determined that normal human telomeres replicate throughout S phase rather than being very late replicating. Furthermore, the overall timing of replication was unaffected by telomere length in young versus old cells or cells whose telomeres had been elongated following transfection with the catalytic subunit of telomerase. Finally, the asymmetry in the length of the G-rich overhang in daughter telomeres produced by leading versus lagging strand synthesis was shown to be established within 1 h of telomere replication, indicating there is no significant delay between synthesis and the processing events that contribute to the establishment of asymmetric overhangs. Therefore, the timings of replication and processing of human telomeres are very different from those of yeast. (C) 1999 Academic Press.