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结局不佳的小鼠:用于研究癌症和衰老中端粒与端粒酶的小鼠模型

Mice with bad ends: mouse models for the study of telomeres and telomerase in cancer and aging.

作者信息

Blasco María A

机构信息

Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Madrid, Spain.

出版信息

EMBO J. 2005 Mar 23;24(6):1095-103. doi: 10.1038/sj.emboj.7600598. Epub 2005 Mar 10.

Abstract

Telomeres are capping structures at the ends of eukaryotic chromosomes, which consist of repetitive DNA bound to an array of specialized proteins. Telomeres are part of the constitutive heterochromatin and are subjected to epigenetic modifications. The function of telomeres is to prevent chromosome ends from being detected as damaged DNA. Both the length of telomere repeats and the integrity of the telomere-binding proteins are important for telomere protection. Telomere length is regulated by telomerase, by the telomere-binding proteins, as well as by activities that modify the state of the chromatin. Various mouse models with altered levels of telomerase activity, or mutant for different telomere-binding proteins, have been recently generated. Here, I will discuss how these different mouse models have contributed to our understanding on the role of telomeres and telomerase in cancer and aging.

摘要

端粒是真核染色体末端的帽状结构,由与一系列特殊蛋白质结合的重复DNA组成。端粒是组成型异染色质的一部分,并经历表观遗传修饰。端粒的功能是防止染色体末端被检测为受损DNA。端粒重复序列的长度和端粒结合蛋白的完整性对于端粒保护都很重要。端粒长度受端粒酶、端粒结合蛋白以及改变染色质状态的活性调控。最近已经产生了各种端粒酶活性水平改变或不同端粒结合蛋白突变的小鼠模型。在此,我将讨论这些不同的小鼠模型如何有助于我们理解端粒和端粒酶在癌症和衰老中的作用。

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本文引用的文献

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The Stability of Broken Ends of Chromosomes in Zea Mays.玉米染色体断头的稳定性
Genetics. 1941 Mar;26(2):234-82. doi: 10.1093/genetics/26.2.234.
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TIN2 mediates functions of TRF2 at human telomeres.TIN2介导TRF2在人类端粒处的功能。
J Biol Chem. 2004 Oct 15;279(42):43799-804. doi: 10.1074/jbc.M408650200. Epub 2004 Aug 3.
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Closed chromatin loops at the ends of chromosomes.染色体末端的封闭染色质环。
J Cell Biol. 2004 Jul 19;166(2):161-5. doi: 10.1083/jcb.200403118. Epub 2004 Jul 12.

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