ArticleNature genetics2023
Thymidine nucleotide metabolism controls human telomere length.
Article in Nature genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT06817590 (Nucleoside Therapy in Patients With Telomere Biology Disorders), which is not on this map. Cited by 42 papers.
What it found
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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.
The trial behind it
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.
Nucleoside Therapy in Patients With Telomere Biology Disorders
Who cites it
42 citing papers in PubMed, 69 citations in OpenAlex.
- How telomere attrition protects against cancer.Nature reviews. Genetics · 2026Review
- The ageing holobiont: crosstalk between telomere dynamics, oxidative stress and the gut microbiome.Biological reviews of the Cambridge Philosophical Society · 2026Review
- Adaptive Regulation of dNTP Homeostasis Confers Osimertinib Resistance in EGFR-Mutant Non-Small Cell Lung Carcinoma.Cancer research · 2026Article
- Saturating variant analysis of TERC redefines the human telomerase reverse transcription mechanism.bioRxiv : the preprint server for biology · 2026Article
- Short telomeres in mitochondrial DNA depletion disorders.Mitochondrion · 2026Article
- Longer leukocyte telomere length increases the odds of premature rupture of membranes: a cross-sectional study based on UK Biobank.Scientific reports · 2026Article
- Polygenic risk and rare variants in endotypes of idiopathic pulmonary fibrosis: a genetic analysis of population-based and case-control cohorts.The Lancet. Respiratory medicine · 2026Article
- Genomic, phenomic and geographic associations of leukocyte telomere length in the United States.Nature genetics · 2026Article
- Rapid loss of viability in acute myeloid leukemia cells upon telomerase inactivation.Blood advances · 2026Article
- Pan-cancer analysis of pyrimidine metabolism reveals signaling pathways connections with chemoresistance role.British journal of cancer · 2026Article
- Diagnosis and management of adult telomere biology disorders.Haematologica · 2026Review
- Nucleotide salvage, genome instability, and potential therapeutic applications.Nucleic acids research · 2026Review
- Integrative profiling of diverse post-translational modifications for prognostic stratification and personalized therapy in papillary thyroid cancer.Frontiers in endocrinology · 2026Article
- Large-scale drug sensitivity, gene dependency, and proteogenomic analyses of telomere maintenance mechanisms in cancer cells.Nature communications · 2025Article
- Therapeutic 6-thio-deoxyguanosine inhibits telomere elongation in cancer cells by inducing a non-productive stalled telomerase complex.Nature communications · 2025Article
- Extension of replicative lifespan by synthetic engineered telomerase RNA in patient induced pluripotent stem cells.Nature biomedical engineering · 2025Article
- Is Telomere Length Optimized in Hatchling Sand Lizards?Evolution & development · 2025Article
- NADCommunications biology · 2025Article
- Identification of biallelic POLA2 variants in two families with an autosomal recessive telomere biology disorder.European journal of human genetics : EJHG · 2025Article
- ERK-USP9X-coupled regulation of thymidine kinase 1 promotes both its enzyme activity-dependent and its enzyme activity-independent functions for tumor growth.Nature structural & molecular biology · 2025Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Telomere length in humans is associated with lifespan and severe diseases, yet the genetic determinants of telomere length remain incompletely defined. Here we performed genome-wide CRISPR-Cas9 functional telomere length screening and identified thymidine (dT) nucleotide metabolism as a limiting factor in human telomere maintenance. Targeted genetic disruption using CRISPR-Cas9 revealed multiple telomere length control points across the thymidine nucleotide metabolism pathway: decreasing dT nucleotide salvage via deletion of the gene encoding nuclear thymidine kinase (TK1) or de novo production by knockout of the thymidylate synthase gene (TYMS) decreased telomere length, whereas inactivation of the deoxynucleoside triphosphohydrolase-encoding gene SAMHD1 lengthened telomeres. Remarkably, supplementation with dT alone drove robust telomere elongation by telomerase in cells, and thymidine triphosphate stimulated telomerase activity in a substrate-independent manner in vitro. In induced pluripotent stem cells derived from patients with genetic telomere biology disorders, dT supplementation or inhibition of SAMHD1 promoted telomere restoration. Our results demonstrate a critical role of thymidine metabolism in controlling human telomerase and telomere length, which may be therapeutically actionable in patients with fatal degenerative diseases.
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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.