ArticleProceedings of the National Academy of Sciences of the United States of America2019
POT1-TPP1 differentially regulates telomerase via POT1 His266 and as a function of single-stranded telomere DNA length.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Pot1b -/- tumors activate G-quadruplex-induced DNA damage to promote telomere hyper-elongation.Nucleic acids research · 2023Article
- The shelterin protein expansion of telomere dynamics: Linking early life adversity, life history, and the hallmarks of aging.Neuroscience and biobehavioral reviews · 2023Review
- Damage-Free Shortening of Telomeres Is a Potential Strategy Supporting Blind Mole-Rat Longevity.Genes · 2023Article
- Small molecule inhibitors of 15-PGDH exploit a physiologic induced-fit closing system.Nature communications · 2023Article
- Telomere maintenance in African trypanosomes.Frontiers in molecular biosciences · 2023Review
- Shelterin reduces the accessibility of telomeric overhangs.Nucleic acids research · 2022Article
- Multiple hPOT1-TPP1 cooperatively unfold contiguous telomeric G-quadruplexes proceeding from 3' toward 5', a feature due to a 3'-end binding preference and to structuring of telomeric DNA.Nucleic acids research · 2021Article
- Arabidopsis retains vertebrate-type telomerase accessory proteins via a plant-specific assembly.Nucleic acids research · 2021Article
- SLX4IP promotes RAP1 SUMOylation by PIAS1 to coordinate telomere maintenance through NF-κB and Notch signaling.Science signaling · 2021Article
- POT1 Regulates Proliferation and Confers Sexual Dimorphism in Glioma.Cancer research · 2021Article
- Active and Passive Destabilization of G-Quadruplex DNA by the Telomere POT1-TPP1 Complex.Journal of molecular biology · 2021Article
- Integrated analysis of telomerase enzymatic activity unravels an association with cancer stemness and proliferation.Nature communications · 2021Article
- Article
- Role of POT1 in Human Cancer.Cancers · 2020Review
- Telomerase Biogenesis and Activities from the Perspective of Its Direct Interacting Partners.Cancers · 2020Review
- Review
- USP7 Is a Master Regulator of Genome Stability.Frontiers in cell and developmental biology · 2020Review
- POT1-TPP1 telomere length regulation and disease.Computational and structural biotechnology journal · 2020Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Telomeres cap the ends of linear chromosomes and terminate in a single-stranded DNA (ssDNA) overhang recognized by POT1-TPP1 heterodimers to help regulate telomere length homeostasis. Here hydroxyl radical footprinting coupled with mass spectrometry was employed to probe protein-protein interactions and conformational changes involved in the assembly of telomere ssDNA substrates of differing lengths bound by POT1-TPP1 heterodimers. Our data identified environmental changes surrounding residue histidine 266 of POT1 that were dependent on telomere ssDNA substrate length. We further determined that the chronic lymphocytic leukemia-associated H266L substitution significantly reduced POT1-TPP1 binding to short ssDNA substrates; however, it only moderately impaired the heterodimer binding to long ssDNA substrates containing multiple protein binding sites. Additionally, we identified a telomerase inhibitory role when several native POT1-TPP1 proteins coat physiologically relevant lengths of telomere ssDNA. This POT1-TPP1 complex-mediated inhibition of telomerase is abrogated in the context of the POT1 H266L mutation, which leads to telomere overextension in a malignant cellular environment.
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Registered trials
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.