TELOMERES SHORTEN DURING AGING OF HUMAN FIBROBLASTS
TELOMERES SHORTEN DURING AGING OF HUMAN FIBROBLASTS
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DOI：
10.1038/345458a0
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发表时间：
1990-05-31
期刊：
影响因子：
64.8
通讯作者：
GREIDER, CW
中科院分区：
文献类型：
--
作者：
HARLEY, CB;FUTCHER, AB;GREIDER, CW
DNA螺旋的末端被称为“阿喀琉斯之踵”。因此，为了防止线性DNA末端可能出现的不完全复制和不稳定，真核生物的染色体在被称为端粒的特殊结构中以特有的重复DNA序列结束。在不朽的细胞中，由于降解或不完全复制而导致的端粒DNA的损失显然由端粒延长来平衡6 - 10，这可能涉及一种称为端粒酶11 - 14的新型DNA聚合酶重新合成额外的重复序列。最近在HeLa细胞中发现了这种聚合酶15。有人提出，正常哺乳动物细胞有限的倍增能力是由于端粒DNA的丢失和基本序列的最终缺失1,16,17。在酵母中，est1突变导致端粒DNA逐渐丢失，最终导致细胞死亡，模拟高级真核细胞的衰老17。在这里，我们表明，人类成纤维细胞的端粒DNA的数量和长度实际上在体外和体内衰老过程中作为序列传代的功能而减少。目前尚不清楚这种DNA丢失是否在衰老中起因果作用。
THE terminus of a DNA helix has been called its Achilles' heel1. Thus to prevent possible incomplete replication2and instability3,4of the termini of linear DNA, eukaryotic chromosomes end in characteristic repetitive DNA sequences within specialized structures called telomeres5. In immortal cells, loss of telomeric DNA due to degradation or incomplete replication is apparently balanced by telomere elongation6–10, which may involvede novosynthesis of additional repeats by a novel DNA polymerase called telomerase11–14. Such a polymerase has been recently detected in HeLa cells15. It has been proposed that the finite doubling capacity of normal mammalian cells is due to a loss of telomeric DNA and eventual deletion of essential sequences1,16,17. In yeast, theest1 mutation causes gradual loss of telomeric DNA and eventual cell death mimicking senescence in higher eukaryotic cells17. Here, we show that the amount and length of telomeric DNA in human fibroblasts does in fact decrease as a function of serial passage during ageingin vitroand possiblyin vivo. It is not known whether this loss of DNA has a causal role in senescence.