Telomeres, chromosome instability and cancer.
Telomeres, chromosome instability and cancer.
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DOI：
10.1093/nar/gkl303
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发表时间：
2006
影响因子：
14.9
通讯作者：
Murnane JP
中科院分区：
文献类型：
--
作者：
Bailey SM;Murnane JP
端粒由重复的富含G的序列和丰富的相关蛋白组成，它们一起形成保护染色体末端的动态帽，并允许它们与有害的DSB区分开来。端粒相关蛋白还具有调节端粒酶的功能，端粒酶是负责添加物种特异性末端重复序列的核糖核蛋白。端粒功能丧失是癌症中常见的染色体不稳定性的重要机制。功能障碍性端粒可以由封端功能所需的端粒相关蛋白的改变引起，或者由促进维持适当端粒结构所需的足够重复序列的逐渐或突然丧失的改变引起。无论机制如何，端粒功能的丧失可导致姐妹染色单体融合和延长的断裂/融合/桥（B/F/B）循环，从而导致广泛的DNA扩增和大的末端缺失。B/F/B循环主要在不稳定染色体获得新的端粒时终止，最常见的是通过其他染色体末端的易位，从而提供了将不稳定性从一条染色体转移到另一条染色体的机制。因此，单个端粒的丢失可导致持续的不稳定性，影响多个染色体，并产生通常与人类癌症相关的许多类型的重排。
Telomeres are composed of repetitive G-rich sequence and an abundance of associated proteins that together form a dynamic cap that protects chromosome ends and allows them to be distinguished from deleterious DSBs. Telomere-associated proteins also function to regulate telomerase, the ribonucleoprtotein responsible for addition of the species-specific terminal repeat sequence. Loss of telomere function is an important mechanism for the chromosome instability commonly found in cancer. Dysfunctional telomeres can result either from alterations in the telomere-associated proteins required for end-capping function, or from alterations that promote the gradual or sudden loss of sufficient repeat sequence necessary to maintain proper telomere structure. Regardless of the mechanism, loss of telomere function can result in sister chromatid fusion and prolonged breakage/fusion/bridge (B/F/B) cycles, leading to extensive DNA amplification and large terminal deletions. B/F/B cycles terminate primarily when the unstable chromosome acquires a new telomere, most often by translocation of the ends of other chromosomes, thereby providing a mechanism for transfer of instability from one chromosome to another. Thus, the loss of a single telomere can result in on-going instability, affect multiple chromosomes, and generate many of the types of rearrangements commonly associated with human cancer.
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影响因子：
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作者：
BRYAN, TM;ENGLEZOU, A;REDDEL, RR
通讯作者：
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影响因子：
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