ArticleThe EMBO journal2019
ATRX loss induces telomere dysfunction and necessitates induction of alternative lengthening of telomeres during human cell immortalization.
Article in The EMBO journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 2 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
85 citing papers in PubMed, 2 syntheses or guidelines pooled it, 121 citations in OpenAlex.
- Congress of Neurological Surgeons systematic review and evidence based guideline on neuropathology for WHO grade II diffuse glioma: update.Journal of neuro-oncology · 2025Pooled it
- Disrupting Mechanisms that Regulate Genomic Repeat Elements to Combat Cancer and Drug Resistance.Frontiers in cell and developmental biology · 2022Pooled it
- Replication stress in cancer: origins, consequences and therapeutic opportunities.Nature reviews. Cancer · 2026Review
- SMARCAL1 is a candidate therapeutic target for ALT-positive tumors.Genes & development · 2026Article
- Article
- Complex structural variations functionally inactivate the telomerase chaperone TCAB1 in osteosarcoma.BMC cancer · 2026Article
- Orphan nuclear receptors recruit TRIM28 to promote telomeric H3K9me3 for the ALT pathway.The EMBO journal · 2026Article
- Review
- Local heterochromatin enrichment promotes telomere clustering and PML nuclear body assembly at telomeres.Cell reports · 2026Article
- Nuclear Mechanics and Nuclear Mechanotransduction in Cancer Cell Migration and Invasion.Biomolecules · 2026Review
- Telomere Crisis Shapes Cancer Evolution.Cold Spring Harbor perspectives in biology · 2026Review
- Optimized primer and model improve precision of X chromosome telomere length determination in the Han population.iScience · 2026Article
- Structural organization and function of telomeric chromatin.Nature cell biology · 2026Review
- From Classical to Emerging Biomarkers of Brain and Central Nervous System Tumors. An Evidence-Based Review with a Focus on Gliomas.Cellular and molecular neurobiology · 2026Review
- DMTF1 up-regulation rescues proliferation defect of telomere dysfunctional neural stem cells via the SWI/SNF-E2F axis.Science advances · 2026Article
- Telomere-driven dysfunctional changes in gynecological cancers: mechanistic insights, biomarker potential, and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- Review
- Phase separated condensates of ATRX regulate neural progenitor identity.Nature communications · 2025Article
- A chromatin-remodeling-independent role for ATRX in protecting centromeric cohesion.The EMBO journal · 2025Article
- Targeting WEE1 Kinase for Breast Cancer Therapeutics: An Update.International journal of molecular sciences · 2025Review
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
Loss of the histone H3.3-specific chaperone component ATRX or its partner DAXX frequently occurs in human cancers that employ alternative lengthening of telomeres (ALT) for chromosomal end protection, yet the underlying mechanism remains unclear. Here, we report that ATRX/DAXX does not serve as an immediate repressive switch for ALT. Instead, ATRX or DAXX depletion gradually induces telomere DNA replication dysfunction that activates not only homology-directed DNA repair responses but also cell cycle checkpoint control. Mechanistically, we demonstrate that this process is contingent on ATRX/DAXX histone chaperone function, independently of telomere length. Combined ATAC-seq and telomere chromatin immunoprecipitation studies reveal that ATRX loss provokes progressive telomere decondensation that culminates in the inception of persistent telomere replication dysfunction. We further show that endogenous telomerase activity cannot overcome telomere dysfunction induced by ATRX loss, leaving telomere repair-based ALT as the only viable mechanism for telomere maintenance during immortalization. Together, these findings implicate ALT activation as an adaptive response to ATRX/DAXX loss-induced telomere replication dysfunction.
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What OpenQuestion holds
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.