ArticleThe Journal of biological chemistry2018
Protection of telomeres 1 proteins POT1a and POT1b can repress ATR signaling by RPA exclusion, but binding to CST limits ATR repression by POT1b.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 42 citations in OpenAlex.
- How telomere attrition protects against cancer.Nature reviews. Genetics · 2026Review
- Fission yeast RPA-TERT-Tpz1TPP1 complex promotes telomere extension and suppresses telomere recombination.PLoS genetics · 2026Article
- Fission yeast RPA-TERT-Tpz1bioRxiv : the preprint server for biology · 2026Article
- Stn1 promotes zebrafish oocyte development via amplifying Wnt/β-catenin signaling.EMBO reports · 2026Article
- Translational Geroscience Strategies for Delaying Multimorbidity.ACS pharmacology & translational science · 2026Review
- REV7 associates with ATRIP and inhibits ATR kinase activity.Nucleic acids research · 2026Article
- Phase separation of hnRNPA1 and TERRA regulates telomeric stability.Journal of molecular cell biology · 2025Article
- Article
- Guardians of the Genome: How the Single-Stranded DNA-Binding Proteins RPA and CST Facilitate Telomere Replication.Biomolecules · 2024Review
- Genome maintenance meets mechanobiology.Chromosoma · 2024Review
- Pot1b -/- tumors activate G-quadruplex-induced DNA damage to promote telomere hyper-elongation.Nucleic acids research · 2023Article
- Human POT1 protects the telomeric ds-ss DNA junction by capping the 5' end of the chromosome.Science (New York, N.Y.) · 2023Article
- Article
- Shelterin is a dimeric complex with extensive structural heterogeneity.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- Telomere dysfunction implicates POT1 in patients with idiopathic pulmonary fibrosis.The Journal of experimental medicine · 2022Article
- Metabolic Alterations in Cellular Senescence: The Role of Citrate in Ageing and Age-Related Disease.International journal of molecular sciences · 2022Review
- Telomeric replication stress: the beginning and the end for alternative lengthening of telomeres cancers.Open biology · 2022Review
- The evolution of metazoan shelterin.Genes & development · 2021Article
- Germline POT1 Deregulation Can Predispose to Myeloid Malignancies in Childhood.International journal of molecular sciences · 2021Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Comprised of telomeric TTAGGG repeats and shelterin, telomeres ensure that the natural ends of chromosomes remain impervious to the DNA damage response. Telomeres carry a long constitutive 3' overhang that can bind replication protein A (RPA) and activate the ATR Ser/Thr kinase (ATR), which induces cell cycle arrest. A single-stranded (ss) TTAGGG repeat-binding protein in mouse shelterin, POT1a, has been proposed to repress ATR signaling by preventing RPA binding. Repression of ATR at telomeres requires tethering of POT1a to the other shelterin subunits situated on the double-stranded (ds) telomeric DNA. The simplest model of ATR repression, the "tethered exclusion model," suggests that the only critical features of POT1a are its connection to shelterin and its binding to ss telomeric DNA. In agreement with the model, we show here that a shelterin-tethered variant of RPA70 (lacking the ATR recruitment domain) can repress ATR signaling at telomeres that lack POT1a. However, arguing against the tethered exclusion model, the nearly identical POT1b subunit of shelterin has been shown to be much less proficient than POT1a in repression of ATR. We now show that POT1b has the intrinsic ability to fully repress ATR but is prevented from doing so when bound to Ctc1, Stn1, Ten1 (CST), the complex needed for telomere end processing. These results establish that shelterin represses ATR with a tethered ssDNA-binding domain that excludes RPA from the 3' overhang and also reveal an unexpected effect of CST on the ability of POT1b to repress ATR.
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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.