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端粒功能障碍、染色体不稳定与癌症

Telomere Dysfunction, Chromosomal Instability and Cancer.

作者信息

Meena Jitendra, Rudolph K Lenhard, Günes Cagatay

机构信息

Leibniz Institute for Age Research, Fritz Lipmann Institute e.V., 07745, Jena, Germany.

出版信息

Recent Results Cancer Res. 2015;200:61-79. doi: 10.1007/978-3-319-20291-4_3.

Abstract

Telomeres form protective caps at the ends of linear chromosomes to prevent nucleolytic degradation, end-to-end fusion, irregular recombination, and chromosomal instability. Telomeres are composed of repetitive DNA sequences (TTAGGG)n in humans, that are bound by specialized telomere binding proteins. Telomeres lose capping function in response to telomere shortening, which occurs during each division of cells that lack telomerase activity-the enzyme that can synthesize telomeres de novo. Telomeres have a dual role in cancer: telomere shortening can lead to induction of chromosomal instability and to the initiation of tumors, however, initiated tumors need to reactivate telomerase in order to stabilize chromosomes and to gain immortal growth capacity. In this review, we summarize current knowledge on the role of telomeres in the maintenance of chromosomal stability and carcinogenesis.

摘要

端粒在线性染色体末端形成保护帽,以防止核酸酶降解、端对端融合、不规则重组和染色体不稳定。在人类中,端粒由重复的DNA序列(TTAGGG)n组成,这些序列与专门的端粒结合蛋白结合。端粒会因端粒缩短而失去封端功能,端粒缩短发生在缺乏端粒酶活性的细胞每次分裂过程中,端粒酶是一种能够从头合成端粒的酶。端粒在癌症中具有双重作用:端粒缩短可导致染色体不稳定并引发肿瘤,然而,起始肿瘤需要重新激活端粒酶,以稳定染色体并获得无限增殖能力。在本综述中,我们总结了关于端粒在维持染色体稳定性和致癌作用中作用的现有知识。

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