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

• Published in: International journal of molecular sciences Vol. 20; no. 13; p. 3186
• Main Authors: Veverka, Pavel, Janovič, Tomáš, Hofr, Ctirad
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28-06-2019; MDPI
• Subjects: Animals; anticancer; Antineoplastic Agents - pharmacology; assembly; Binding sites; Cancer; Cell cycle; Chromosomes; Deoxyribonucleic acid; DNA; DNA-binding protein; Domains; Electron microscopy; Enzyme Inhibitors - pharmacology; Humans; Immortalization; inhibitor; Microscopy; Mutation; Nucleotide sequence; Protein Binding; protein-DNA interaction; protein-protein interaction; Proteins; quantitative biology; Review; RNA-directed DNA polymerase; shelterin; Telomerase; Telomerase - antagonists & inhibitors; Telomerase - chemistry; Telomerase - metabolism; telomere; Telomere-Binding Proteins - chemistry; Telomere-Binding Proteins - metabolism; Tumor cells; Tumors; shelterin; telomerase; inhibitor; telomere; assembly; protein-DNA interaction; protein-protein interaction; quantitative biology; anticancer
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20133186

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.