ArticleGenes & development2014
TRF1 negotiates TTAGGG repeat-associated replication problems by recruiting the BLM helicase and the TPP1/POT1 repressor of ATR signaling.
Article in Genes & development, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers.
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Who cites it
130 citing papers in PubMed, 187 citations in OpenAlex.
- Beyond End Protection: Shelterin, POT1 Dysfunction, and Telomere Replication Stress in Cancer.Biomolecules · 2026Review
- Inhibition of lagging strand replication by G-rich telomeric DNA and the shelterin subunit POT1.The EMBO journal · 2026Article
- Cancer-associated TRF1 mutations alter PARP1 interaction dynamics: an in silico study.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- ESCO2 Interacts with TRF1/2 and Facilitates Telomere Maintenance.International journal of molecular sciences · 2026Article
- Decoding the significance of TERT gene in Polycystic Ovary Syndrome: From molecular mechanisms to emerging diagnostic and therapeutic strategies.Journal of ovarian research · 2026Review
- BLM and FANCJ role in the response to G-quadruplex-dependent telomeric replicative stress.Communications biology · 2026Article
- TRF1 and TRF2 form distinct shelterin subcomplexes at telomeres.Cell reports · 2025Article
- TRF1 relies on fork reversal to prevent fragility at human telomeres.Nature communications · 2025Article
- SLX4IP acts in parallel to FANCM to limit BLM-dependent replication stress at ALT telomeres.bioRxiv : the preprint server for biology · 2025Article
- A CPC-shelterin-BTR axis regulates mitotic telomere deprotection.Nature communications · 2025Article
- A Review of Telomere Attrition in Cancer and Aging: Current Molecular Insights and Future Therapeutic Approaches.Cancers · 2025Review
- The truncated isoform of the receptor for hyaluronan-mediated motility (RHAMMFrontiers in aging · 2025Article
- Ustilago maydis Trf2 ensures genome stability by antagonizing Blm-mediated telomere recombination: Fine-tuning DNA repair factor activity at telomeres through opposing regulations.PLoS genetics · 2024Article
- Structural biology of shelterin and telomeric chromatin: the pieces and an unfinished puzzle.Biochemical Society transactions · 2024Review
- Fate of telomere entanglements is dictated by the timing of anaphase midregion nuclear envelope breakdown.Nature communications · 2024Article
- Replication stress as a driver of cellular senescence and aging.Communications biology · 2024Review
- Human telomere length is chromosome end-specific and conserved across individuals.Science (New York, N.Y.) · 2024Article
- Deregulated DNA ADP-ribosylation impairs telomere replication.Nature structural & molecular biology · 2024Article
- PARP2 promotes Break Induced Replication-mediated telomere fragility in response to replication stress.Nature communications · 2024Article
- Mitochondria and telomeres: hand in glove.Biogerontology · 2024Review
70 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The semiconservative replication of telomeres is facilitated by the shelterin component TRF1. Without TRF1, replication forks stall in the telomeric repeats, leading to ATR kinase signaling upon S-phase progression, fragile metaphase telomeres that resemble the common fragile sites (CFSs), and the association of sister telomeres. In contrast, TRF1 does not contribute significantly to the end protection functions of shelterin. We addressed the mechanism of TRF1 action using mouse conditional knockouts of BLM, TRF1, TPP1, and Rap1 in combination with expression of TRF1 and TIN2 mutants. The data establish that TRF1 binds BLM to facilitate lagging but not leading strand telomeric DNA synthesis. As the template for lagging strand telomeric DNA synthesis is the TTAGGG repeat strand, TRF1-bound BLM is likely required to remove secondary structures formed by these sequences. In addition, the data establish that TRF1 deploys TIN2 and the TPP1/POT1 heterodimers in shelterin to prevent ATR during telomere replication and repress the accompanying sister telomere associations. Thus, TRF1 uses two distinct mechanisms to promote replication of telomeric DNA and circumvent the consequences of replication stress. These data are relevant to the expression of CFSs and provide insights into TIN2, which is compromised in dyskeratosis congenita (DC) and related disorders.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.