Multi-step coordination of telomerase recruitment in fission yeast through two coupled telomere-telomerase interfaces
| العنوان: | Multi-step coordination of telomerase recruitment in fission yeast through two coupled telomere-telomerase interfaces |
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| المؤلفون: | Feng Qiao, Xichan Hu, Hyun Ik Jun, Jin-Kwang Kim, Jinqiang Liu |
| المصدر: | eLife Hu, X; Liu, J; Jun, H-I; Kim, J-K; & Qiao, F. (2016). Multi-step coordination of telomerase recruitment in fission yeast through two coupled telomere-telomerase interfaces. ELIFE, 5. doi: 10.7554/eLife.15470. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/6gh8498kTest eLife, Vol 5 (2016) |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Telomerase, Sequence Homology, medicine.disease_cause, Shelterin Complex, Nucleotidases, Biology (General), Phosphorylation, genes, Mutation, biology, General Neuroscience, Cell Cycle, General Medicine, Cell cycle, Telomere, Protein-Serine-Threonine Kinases, Cell biology, Genes and Chromosomes, Medicine, Schizosaccharomyces, Research Article, chromosomes, QH301-705.5, Science, Telomere-Binding Proteins, Protein Serine-Threonine Kinases, DNA replication, telomerase, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Telomerase RNA component, medicine, Amino Acid Sequence, 030102 biochemistry & molecular biology, General Immunology and Microbiology, biology.organism_classification, Shelterin, telomeres, Molecular biology, Checkpoint Kinase 2, 030104 developmental biology, recruitment, Biochemistry and Cell Biology, Schizosaccharomyces pombe Proteins, S. pombe |
| الوصف: | Tightly controlled recruitment of telomerase, a low-abundance enzyme, to telomeres is essential for regulated telomere synthesis. Recent studies in human cells revealed that a patch of amino acids in the shelterin component TPP1, called the TEL-patch, is essential for recruiting telomerase to telomeres. However, how TEL-patch—telomerase interaction integrates into the overall orchestration of telomerase regulation at telomeres is unclear. In fission yeast, Tel1ATM/Rad3ATR-mediated phosphorylation of shelterin component Ccq1 during late S phase is involved in telomerase recruitment through promoting the binding of Ccq1 to a telomerase accessory protein Est1. Here, we identify the TEL-patch in Tpz1TPP1, mutations of which lead to decreased telomeric association of telomerase, similar to the phosphorylation-defective Ccq1. Furthermore, we find that telomerase action at telomeres requires formation and resolution of an intermediate state, in which the cell cycle-dependent Ccq1-Est1 interaction is coupled to the TEL-patch—Trt1 interaction, to achieve temporally regulated telomerase elongation of telomeres. DOI: http://dx.doi.org/10.7554/eLife.15470.001Test eLife digest The genetic blueprints for animals, plants and fungi are mostly contained within long strands of DNA and packaged into more compact thread-like structures called chromosomes. As such, most cells need to duplicate their chromosomes before they divide so that the two new cells each get a complete set of genetic instructions. The machinery that copies DNA is unable to make it to the very ends of the chromosomes. Instead, an enzyme called telomerase adds new DNA to the chromosome ends to prevent them becoming too short. Problems with this process can cause serious issues, such as cell death or cancer, and so the activity of telomerase is carefully controlled. Other proteins guide telomerase to the ends of the chromosome only after the rest of the DNA has been copied. However, scientists do not know exactly how cells correctly time the arrival of telomerase. A group of proteins called shelterin protects the chromosome ends, and studies with human cells have shown that telomerase attaches to a specific patch on one of shelterin proteins, called the TEL-patch, to begin its work. Now, Hu, Liu et al. have identified a similar TEL-patch in a shelterin protein from a type of yeast called fission yeast; this patch is also needed to attach telomerase to the chromosome ends. Further experiments with this yeast then showed that telomerase only arrives at the ends of the chromosomes after two parallel interaction interfaces have formed. Importantly, one of these interactions only takes place after most of the chromosomes are have been copied. As such, this “two-pronged interaction” mechanism ensures that the telomerase enzyme arrives at the end of the chromosomes at the right time. Other similarities between human and fission yeast chromosome ends make it plausible that a comparable process controls the timing of telomerase attachment in human cells. However, more studies will be needed to confirm if this is the case. DOI: http://dx.doi.org/10.7554/eLife.15470.002Test |
| وصف الملف: | application/pdf |
| تدمد: | 2050-084X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::325bd181ac971b383dfcc0771b8c2356Test https://pubmed.ncbi.nlm.nih.gov/27253066Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....325bd181ac971b383dfcc0771b8c2356 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2050084X |
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