The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
POT1 protects telomeres from a transient DNA damage response and determines how human chromosomes end
Open accessAbstract
The hallmarks of telomere dysfunction in mammals are reduced telomeric 3' overhangs, telomere fusions, and cell cycle arrest due to a DNA damage response. Here, we report on the phenotypes of RNAi-mediated inhibition of POT1, the single-stranded telomeric DNA-binding protein. A 10-fold reduction in POT1 protein in tumor cells induced neither telomere fusions nor cell cycle arrest. However, the 3' overhang DNA was reduced and all telomeres elicited a transient DNA damage response in G1, indicating that extensive telomere damage can occur without cell cycle arrest or telomere fusions. RNAi to POT1 also revealed its role in generating the correct sequence at chromosome ends. The recessed 5' end of the telomere, which normally ends on the sequence ATC-5', was changed to a random position within the AATCCC repeat. Thus, POT1 determines the structure of the 3' and 5' ends of human chromosomes, and its inhibition generates a novel combination of telomere dysfunction phenotypes in which chromosome ends behave transiently as sites of DNA damage, yet remain protected from nonhomologous end-joining.
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“POT1 and TPP1 serve a role in protecting the single-stranded portion of the telomere because loss of POT1 impairs telomere capping (16)(17)(18)(19).”
From Telomeres and telomerase in cancer (2010) · cites this paper as [16]
In the citing paper
“Due to the mechanism of replication, telomeres shorten with every cell division, ticking as a cellular “molecular clock” [2-8].”
From Markers of cellular senescence. Telomere shortening as a marker of cellular senescence (2016) · cites this paper as [5]
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Shelterin: the protein complex that shapes and safeguards human telomeres
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Metadata
- Authors
- Hockemeyer, D., Sfeir, A. J., Shay, J. W., Wright, W. E., & de Lange, T.
- Affiliations
- Rockefeller University (US)
- The University of Texas Southwestern Medical Center (US)
- Venue
- The EMBO Journal
- Published
- 2005-06-23
- Volume
- 24
- Issue
- 14
- Pages
- 2667-2678
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1176460
- OpenAlex
- W2138398263
- Cited by
- 314
- References
- 34
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 9 · 2023: 11 · 2022: 3 · 2021: 7 · 2020: 16 · 2019: 11 · 2018: 6 · 2017: 15 · 2016: 14 · 2015: 13 · 2014: 21 · 2013: 13 · 2012: 21
- FWCI
- 12.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense
- Ellison Medical Foundation
- National Institutes of Health ((AG01228), GM49046)
- National Institute on Aging (R56AG016642, AG 01228, AG16642, R01AG001228, R01AG016642)
- National Institute of General Medical Sciences (GM 49046, R37GM049046, R01GM049046)
- 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
- POT1, telomere dysfunction, DNA damage response, chromosome ends, telomere fusion, cell cycle arrest, non-homologous end joining, telomeric repeats, RNAi knockdown, cancer cells
- MeSH terms
- Shelterin Complex, Chromosomes, Human, DNA Damage, HeLa Cells, Humans, Telomere, Alternative Splicing, Protein Isoforms, Telomere-Binding Proteins, Cell Proliferation
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