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Super-Resolution Fluorescence Imaging of Telomeres Reveals TRF2-Dependent T-loop Formation
Open accessAbstract
We have applied a super-resolution fluorescence imaging method, stochastic optical reconstruction microscopy (STORM), to visualize the structure of functional telomeres and telomeres rendered dysfunctional through removal of shelterin proteins. The STORM images showed that functional telomeres frequently exhibit a t-loop configuration. Conditional deletion of individual components of shelterin showed that TRF2 was required for the formation and/or maintenance of t-loops, whereas deletion of TRF1, Rap1, or the POT1 proteins (POT1a and POT1b) had no effect on the frequency of t-loop occurrence. Within the shelterin complex, TRF2 uniquely serves to protect telomeres from two pathways that are initiated on free DNA ends: classical nonhomologous end-joining (NHEJ) and ATM-dependent DNA damage signaling. The TRF2-dependent remodeling of telomeres into t-loop structures, which sequester the ends of chromosomes, can explain why NHEJ and the ATM signaling pathway are repressed when TRF2 is present.
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“Telomeres are repetitive DNA sequences, bound by the six-subunit shelterin complex [86] that facilitates the formation of telomere loops (t-loop) to hide the telomere end [87,88], thus protecting the natural chromosome ends from signaling pathways that sense and act at DNA breaks.”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [88]
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“In agreement, TRF2 overexpression delays replicative senescence onset [101], indicating that TRF2 capacity to sequester the telomere terminus via the t-loop conformation [88] might suppress the DNA damage signal from too short telomere ends and protect them from ATM signaling.”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [88]
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Metadata
- Authors
- Doksani, Y., Wu, J. Y., de Lange, T., & Zhuang, X.
- Affiliations
- Rockefeller University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Zhuang, Xiaowei
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 155
- Issue
- 2
- Pages
- 345-356
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4062873
- OpenAlex
- W2164580633
- Cited by
- 493
- References
- 69
- Citations by year
- 2026: 12 · 2025: 21 · 2024: 46 · 2023: 36 · 2022: 31 · 2021: 51 · 2020: 40 · 2019: 37 · 2018: 47 · 2017: 42 · 2016: 45 · 2015: 45 · 2014: 36 · 2013: 4
- FWCI
- 30.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute on Aging (R56AG016642, AG016642, R01AG016642)
- National Institute of General Medical Sciences (R01GM068518, R37GM049046, R01GM049046, GM 068518, GM096450, R01GM096450, GM049046)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- telomeres, T-loop, TRF2, shelterin, TRF1, Rap1, POT1, super-resolution fluorescence microscopy, storms, non-homologous end joining, ATM signaling, DNA damage response, telomere dysfunction, telomere protection
- MeSH terms
- Shelterin Complex, Animals, DNA-Binding Proteins, Fibroblasts, Microscopy, Fluorescence, Telomere, Telomere-Binding Proteins, Telomeric Repeat Binding Protein 2, Mice
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