ArticleNucleic acids research2021
TIN2 is an architectural protein that facilitates TRF2-mediated trans- and cis-interactions on telomeric DNA.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- Genomic and computational analysis of variants in telomere regulatory genes in subjects with bone marrow failure.European journal of human genetics : EJHG · 2026Article
- Review
- Targeting Telomere Shelterin Protein TPP1 with Elbasvir: Induction of Autophagy and Suppression of Esophageal Cancer Tumorigenesis.Anti-cancer agents in medicinal chemistry · 2026Article
- The Interplay Between Obesity and Type 2 Diabetes: Common Pathophysiological Mechanisms Contributing to Telomere Shortening.Life (Basel, Switzerland) · 2025Review
- Identification of telomere maintenance-driven molecular subtypes in hepatocellular carcinoma: implications for prognosis and targeted therapy via KPNA2.Discover oncology · 2025Article
- C-Terminal Extended Domain-Independent Telomere Maintenance: Modeling the Function of TIN2 Isoforms inInternational journal of molecular sciences · 2025Article
- Recent progress in human telomerase structure and its therapeutic targeting.Frontiers in molecular biosciences · 2025Review
- The molecular mechanism for TERRA recruitment and annealing to telomeres.Nucleic acids research · 2024Article
- TRF1 and TRF2: pioneering targets in telomere-based cancer therapy.Journal of cancer research and clinical oncology · 2024Review
- Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases.Redox biology · 2024Review
- Single-molecule imaging of genome maintenance proteins encountering specific DNA sequences and structures.DNA repair · 2023Review
- Phosphorylation of TRF2 promotes its interaction with TIN2 and regulates DNA damage response at telomeres.Nucleic acids research · 2023Article
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
The telomere specific shelterin complex, which includes TRF1, TRF2, RAP1, TIN2, TPP1 and POT1, prevents spurious recognition of telomeres as double-strand DNA breaks and regulates telomerase and DNA repair activities at telomeres. TIN2 is a key component of the shelterin complex that directly interacts with TRF1, TRF2 and TPP1. In vivo, the large majority of TRF1 and TRF2 are in complex with TIN2 but without TPP1 and POT1. Since knockdown of TIN2 also removes TRF1 and TRF2 from telomeres, previous cell-based assays only provide information on downstream effects after the loss of TRF1/TRF2 and TIN2. Here, we investigated DNA structures promoted by TRF2-TIN2 using single-molecule imaging platforms, including tracking of compaction of long mouse telomeric DNA using fluorescence imaging, atomic force microscopy (AFM) imaging of protein-DNA structures, and monitoring of DNA-DNA and DNA-RNA bridging using the DNA tightrope assay. These techniques enabled us to uncover previously unknown unique activities of TIN2. TIN2S and TIN2L isoforms facilitate TRF2-mediated telomeric DNA compaction (cis-interactions), dsDNA-dsDNA, dsDNA-ssDNA and dsDNA-ssRNA bridging (trans-interactions). Furthermore, TIN2 facilitates TRF2-mediated T-loop formation. We propose a molecular model in which TIN2 functions as an architectural protein to promote TRF2-mediated trans and cis higher-order nucleic acid structures at telomeres.
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Registered trials
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