Processive and distributive extension of human telomeres by telomerase under homeostatic and nonequilibrium conditions.
Processive and distributive extension of human telomeres by telomerase under homeostatic and nonequilibrium conditions.
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DOI：
10.1016/j.molcel.2011.03.020
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发表时间：
2011-05-06
期刊：
影响因子：
16
通讯作者：
Wright WE
中科院分区：
文献类型：
--
作者：
Zhao Y;Abreu E;Kim J;Stadler G;Eskiocak U;Terns MP;Terns RM;Shay JW;Wright WE
关于端粒酶在体内如何作用的特定信息对于了解人类肿瘤细胞的端粒动力学是必要的。我们的结果表明，在维持端粒长度的条件下，在每个细胞分裂过程中，每个端粒上只有一个端粒酶分子起作用，并在每一端增加~60个核苷酸。相反，当端粒伸长时，多个端粒酶分子作用于每个端粒(非平衡条件)。在用端粒酶抑制剂GRN163L进行的长期治疗逆转后的最初几周，端粒酶延长的过程较少，此时Cajal小体无法将端粒酶RNA传递到端粒。这一结果表明，Cajal小体对端粒酶的加工可能会影响其加工能力。过度表达的端粒酶也比内源性表达的端粒酶进行得更少。这些发现揭示了体内端粒酶采用的两种不同的主要延伸方式。
Specific information about how telomerase acts in vivo is necessary for understanding telomere dynamics in human tumor cells. Our results imply that under homeostatic telomere length-maintenance conditions only one molecule of telomerase acts at each telomere during every cell division and processively adds ~60 nt to each end. In contrast, multiple molecules of telomerase act at each telomere when telomeres are elongating (non-equilibrium conditions). Telomerase extension is less processive during the first few weeks following the reversal of long-term treatment with the telomerase inhibitor GRN163L, a time when Cajal bodies fail to deliver telomerase RNA to telomeres. This result implies that processing of telomerase by Cajal bodies may affect its processivity. Overexpressed telomerase is also less processive than the endogenously expressed telomerase. These findings reveal two major distinct extension modes adopted by telomerase in vivo.
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影响因子：
64.5
作者：
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通讯作者：
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