Lomonosov Moscow State University, Chemistry Faculty, Moscow, 119991, Russia.
Biochemistry (Mosc). 2015 Mar;80(3):251-9. doi: 10.1134/S0006297915030013.
The activity of telomerase allows eukaryotic cells to have unlimited division potential. On its functioning, telomerase synthesizes short DNA repeats at the 3'-end of DNA within chromosomes that ensures genome stability during cell division. Telomerase is active in the majority of cancer cell types and is virtually absent in somatic cells with rare exceptions. This difference allows us to consider inhibition of telomerase activity as a possible approach to antitumor therapy. Telomerase is a nucleoprotein composed of two main components: the reverse transcriptase (hTERT), which is a catalytic subunit, and telomerase RNA (hTR), which encodes a template for synthesis of repeats. The biogenesis and features of telomerase seem very promising for its inhibition due to complementary interactions. In this review, we analyze putative pathways of oligonucleotide influence on telomerase and consider the known native and modified oligonucleotide inhibitors of telomerase, as well as possible mechanisms of their action. We also discuss the application of telomerase-targeted oligonucleotide conjugates for in vivo imaging of tumor cells.
端粒酶的活性使真核细胞具有无限的分裂潜能。端粒酶在其功能上，在染色体中 DNA 的 3'末端合成短的 DNA 重复序列，从而确保细胞分裂过程中基因组的稳定性。端粒酶在大多数癌细胞类型中活跃，而在体细胞中几乎不存在，只有极少数例外。这种差异使我们能够考虑抑制端粒酶活性作为抗肿瘤治疗的一种可能方法。端粒酶是一种由两个主要成分组成的核蛋白：逆转录酶（hTERT），它是一种催化亚基，和端粒酶 RNA（hTR），它编码重复合成的模板。端粒酶的生物发生和特征因其互补相互作用而非常有希望用于其抑制。在这篇综述中，我们分析了寡核苷酸对端粒酶影响的可能途径，并考虑了已知的天然和修饰的端粒酶寡核苷酸抑制剂，以及它们作用的可能机制。我们还讨论了端粒酶靶向寡核苷酸偶联物在肿瘤细胞体内成像中的应用。
