TRF1 binds a bipartite telomeric site with extreme spatial flexibility
Open accessAbstract
TRF1 is a key player in telomere length regulation. Because length control was proposed to depend on the architecture of telomeres, we studied how TRF1 binds telomeric TTAGGG repeat DNA and alters its conformation. Although the single Myb-type helix-turn-helix motif of a TRF1 monomer can interact with telomeric DNA, TRF1 predominantly binds as a homodimer. Systematic Evolution of Ligands by Exponential enrichment (SELEX) with dimeric TRF1 revealed a bipartite telomeric recognition site with extreme spatial variability. Optimal sites have two copies of a 5'-YTAGGGTTR-3' half-site positioned without constraint on distance or orientation. Analysis of binding affinities and DNase I footprinting showed that both half-sites are simultaneously contacted by the TRF1 dimer, and electron microscopy revealed looping of the intervening DNA. We propose that a flexible segment in TRF1 allows the two Myb domains of the homodimer to interact independently with variably positioned half-sites. This unusual DNA binding mode is directly relevant to the proposed architectural role of TRF1.
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TRF1 has the ability to induce bending, looping, and pairing of duplex telomeric DNA.
“TRF1 has the ability to induce bending, looping, and pairing of duplex telomeric DNA (5, 6, 20, 21), activities that could facilitate the folding back of the telomere.”
From Control of Human Telomere Length by TRF1 and TRF2 (2000) · cites this paper as [6]
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- Authors
- Bianchi, A., Stansel, R. M., Fairall, L., Griffith, J. D., Rhodes, D., & de Lange, T.
- Affiliations
- University of Geneva (CH)
- University of North Carolina at Chapel Hill (US)
- MRC Laboratory of Molecular Biology (GB)
- Venue
- The EMBO Journal
- Published
- 1999-10-15
- Volume
- 18
- Issue
- 20
- Pages
- 5735-5744
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1171640
- OpenAlex
- W2103202621
- Cited by
- 217
- References
- 52
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 8 · 2023: 3 · 2022: 5 · 2021: 7 · 2020: 5 · 2019: 4 · 2018: 7 · 2017: 8 · 2016: 7 · 2015: 4 · 2014: 11 · 2013: 9 · 2012: 12
- FWCI
- 6.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- Sussex Research Online (University of Sussex) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- UNC Libraries
- Funders
- National Institutes of Health (5r01ca070343-04, GM49046)
- National Cancer Institute (CA70343)
- National Institute of General Medical Sciences (GM 49046, GM-31819, R01GM031819)
- Topics
- Health Sciences › Medicine › Physiology › 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 › Genomics and Chromatin Dynamics
- Keywords
- TRF1, telomere length regulation, telomeric DNA binding, TTAGGG repeats, DNA conformation, DNA looping, SELEX, DNase I footprinting, electron microscopy
- MeSH terms
- Base Sequence, Binding Sites, DNA, DNA-Binding Proteins, Humans, Ligands, Microscopy, Electron, Models, Molecular, Molecular Sequence Data, Polymerase Chain Reaction, Telomere, DNA Primers, Dimerization, Proto-Oncogene Proteins c-myb, Protein Structure, Quaternary, Telomeric Repeat Binding Protein 1, In Vitro Techniques
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