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Quantitative Biology of Human Shelterin and Telomerase: Searching for the Weakest Point

LifeB, Chromatin Molecular Complexes, CEITEC and Functional Genomics and Proteomics, National Centre for Biomolecular Research, Faculty of Science, Masaryk University, CZ-62500 Brno, Czech Republic
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Int. J. Mol. Sci. 2019, 20(13), 3186; https://doi.org/10.3390/ijms20133186
Received: 30 April 2019 / Revised: 12 June 2019 / Accepted: 27 June 2019 / Published: 28 June 2019
(This article belongs to the Special Issue Role of Telomeres and Telomerase in Cancer and Aging 2019)
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Abstract

The repetitive telomeric DNA at chromosome ends is protected from unwanted repair by telomere-associated proteins, which form the shelterin complex in mammals. Recent works have provided new insights into the mechanisms of how human shelterin assembles and recruits telomerase to telomeres. Inhibition of telomerase activity and telomerase recruitment to chromosome ends is a promising target for anticancer therapy. Here, we summarize results of quantitative assessments and newly emerged structural information along with the status of the most promising approaches to telomerase inhibition in cancer cells. We focus on the mechanism of shelterin assembly and the mechanisms of how shelterin affects telomerase recruitment to telomeres, addressing the conceptual dilemma of how shelterin allows telomerase action and regulates other essential processes. We evaluate how the identified critical interactions of telomerase and shelterin might be elucidated in future research of new anticancer strategies. View Full-Text
Keywords: telomerase; shelterin; telomere; quantitative biology; protein-protein interaction; protein-DNA interaction; assembly; inhibitor; anticancer telomerase; shelterin; telomere; quantitative biology; protein-protein interaction; protein-DNA interaction; assembly; inhibitor; anticancer
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Veverka, P.; Janovič, T.; Hofr, C. Quantitative Biology of Human Shelterin and Telomerase: Searching for the Weakest Point. Int. J. Mol. Sci. 2019, 20, 3186.

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