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Protection of mammalian telomeres
Abstract
Telomeres allow cells to distinguish natural chromosome ends from damaged DNA. When telomere function is disrupted, a potentially lethal DNA damage response can ensue, DNA repair activities threaten the integrity of chromosome ends, and extensive genome instability can arise. It is not clear exactly how the structure of telomere ends differs from sites of DNA damage and how telomeres protect chromosome ends from DNA repair activities. What are the defining structural features of telomeres and through which mechanisms do they ensure chromosome end protection? What is the molecular basis of the telomeric cap and how does it act to sequester the chromosome end? Here I discuss data gathered in the last few years, suggesting that the protection of human chromosome ends primarily depends on the telomeric protein TRF2 and that telomere capping involves the formation of a higher order structure, the telomeric loop or t-loop.
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“In mammalian cells, the ends of the chromosomes consist of a terminal 3′ single-stranded tail, the G strand overhang, which is buried into adjacent double-stranded repetitive telomeric DNA, forming a protective “t loop” higher-order structure (de Lange, 2002”
From DNA Repair, Genome Stability, and Aging (2005) · cites this paper as de Lange, 2002
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The human telomeric protein hTRF1 induces telomere-specific nucleosome mobility
Pisano, S., Leoni, D., Galati, A., Rhodes, D., Savino, M., & Cacchione, S. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkp1228 · Cited by 40
Tseng, S., Shen, Z.-J., Tsai, H.-J., Lin, Y., & Teng, S. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp235 · Cited by 39
Telomeric DNA Ends Are Essential for the Localization of Ku at Telomeres in Fission Yeast
Miyoshi, T., Sadaie, M., Kanoh, J., & Ishikawa, F. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m208813200 · Cited by 39
Which end: dissecting Ku's function at telomeres and double-strand breaks: Figure 1.Preprint
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Metadata
- Authors
- de Lange, T.
- Venue
- Oncogene
- Published
- 2002-01-21
- Volume
- 21
- Issue
- 4
- Pages
- 532-540
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W1541877559
- Cited by
- 942
- References
- 77
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 13 · 2023: 12 · 2022: 14 · 2021: 15 · 2020: 19 · 2019: 27 · 2018: 18 · 2017: 28 · 2016: 29 · 2015: 26 · 2014: 41 · 2013: 36 · 2012: 36
- FWCI
- 12.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- telomeres, telomere capping, chromosome end protection, TRF2, T-loop, DNA damage response, DNA repair, genomic instability, telomere structure, telomere length
- MeSH terms
- Ku Autoantigen, Animals, Chromosome Aberrations, DNA Helicases, DNA-Binding Proteins, Humans, Models, Genetic, Nuclear Proteins, Nucleic Acid Conformation, Recombination, Genetic, Yeasts, Telomere, Cellular Senescence, Apoptosis, Protein Serine-Threonine Kinases, Saccharomyces cerevisiae Proteins, Antigens, Nuclear, Telomeric Repeat Binding Protein 2, DNA-Activated Protein Kinase
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