Telomerase structure function

Telomerase structure function
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DOI:
10.1016/j.sbi.2010.11.005
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发表时间:
2011-02-01
影响因子:
6.8
通讯作者:
Skordalakes, Emmanuel
Skordalakes, Emmanuel
中科院分区:
生物学2区
文献类型:
--
作者:
Mason, Mark;Schuller, Anthony;Skordalakes, Emmanuel

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端粒及其相关蛋白是线性染色体末端的特化结构,其作为保护DNA免受可能导致基因组不稳定性的核酸外切酶降解和重组事件的帽起作用。在这篇综述中,我们讨论了最近的出版物描述的高分辨率结构的个别域和全长的端粒酶催化亚基单独和复杂的假定的RNA模板和端粒DNA。这些结构,连同现有的生化数据,提供了新的见解端粒复制和长度的端粒酶稳态的基本机制。此外,这些数据进一步丰富了我们对聚合酶DNA复制机制的理解,并为设计可能对癌症和其他与细胞衰老相关的疾病具有治疗价值的端粒酶小分子抑制剂提供了框架。
Telomeres and their associated proteins are specialized structures at the ends of linear chromosomes that function as caps that protect the DNA from exonuclease degradation and recombination events that could lead to genomic instability. In this review, we discuss recent publications describing the high-resolution structures of individual domains and of the full-length catalytic subunit of telomerase alone and in complex with its putative RNA template and telomeric DNA. These structures, together with existing biochemical data, provide novel insights into the basic mechanism of telomere replication and length homeostasis by telomerase. Moreover, these data further enrich our understanding of the mechanism of DNA replication by polymerases in general and they provide a framework to design small molecule inhibitors of telomerase that may be of therapeutic value for cancer and other diseases associated with cellular aging.