Telomere shortening is proportional to the size of the G-rich telomeric 3′-overhang

Telomere shortening is proportional to the size of the G-rich telomeric 3′-overhang
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DOI:
10.1074/jbc.m002843200
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发表时间:
2000-06-30
影响因子:
4.8
通讯作者:
Wright, WE
Wright, WE
中科院分区:
生物学2区
文献类型:
--
作者:
Huffman, KE;Levene, SD;Wright, WE

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大多数正常的二倍体人类细胞不表达端粒酶活性,并且不能在进行细胞分裂时维持端粒长度。我们发现,在四种人类细胞类型中,富含G的单链端粒3 '-突出端的长度与端粒缩短的速率成正比,这四种人类细胞类型在培养中表现出不同的端粒缩短速率。这些结果提供了直接的证据表明,G丰富的悬垂的大小是不固定的,但受到监管。操纵这一速率的潜在能力对于减缓正常细胞中的复制老化速率和与抗端粒酶疗法组合加速癌细胞中的端粒损失速率都具有深远的意义。
Most normal diploid human cells do not express telomerase activity and are unable to maintain telomere length with ongoing cell divisions. We show that the length of the single-stranded G-rich telomeric 3'-overhang is proportional to the rate of shortening in four human cell types that exhibit different rates of telomere shortening in culture. These results provide direct evidence that the size of the G-rich overhang is not fixed but subject to regulation. The potential ability to manipulate this rate has profound implications both for slowing the rate of replicative aging in normal cells and for accelerating the rate of telomere loss in cancer cells in combination with anti-telomerase therapies.