ArticleNature communications2023
A non-genetic switch triggers alternative telomere lengthening and cellular immortalization in ATRX deficient cells.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Twisting the End Game: How Telomere Chromatin Modifications Shape Telomere Maintenance.Aging cell · 2026Review
- SMARCAL1 is a candidate therapeutic target for ALT-positive tumors.Genes & development · 2026Article
- Cancer and aging: complex associations and therapeutic targets.Molecular biomedicine · 2026Review
- Structural organization and function of telomeric chromatin.Nature cell biology · 2026Review
- From Permits to Samples: Addressing Key Challenges for High-Quality Reference Genome Generation in Europe.Molecular ecology resources · 2026Review
- ATRX safeguards cellular identity duringbioRxiv : the preprint server for biology · 2026Article
- Chaperonin proteins CCT5 and CCT7 epigenetically restrict the transition from pluripotency to totipotency in embryonic stem cells.Stem cell reports · 2026Article
- Loss of function ofiScience · 2025Article
- Alternative lengthening of telomere-based immortalization renders H3G34R-mutant diffuse hemispheric glioma hypersensitive to PARP inhibitor combination regimens.Neuro-oncology · 2025Article
- Biomolecular Condensates in Telomere Maintenance of ALT Cancer Cells.Journal of molecular biology · 2025Review
- Neotelomeres and telomere-spanning chromosomal arm fusions in cancer genomes revealed by long-read sequencing.Cell genomics · 2024Article
- Mechanisms of telomere maintenance and associated therapeutic vulnerabilities in malignant gliomas.Neuro-oncology · 2024Review
- Accelerating 3D genomics data analysis with Microcket.Communications biology · 2024Article
- BLM helicase unwinds lagging strand substrates to assemble the ALT telomere damage response.Molecular cell · 2024Article
- Genome maintenance meets mechanobiology.Chromosoma · 2024Review
- Inhibition of p53 and ATRX increases telomeric recombination in primary fibroblasts.FEBS open bio · 2023Article
- Switching on cancer survival mechanisms.Nature reviews. Cancer · 2023Article
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alternative Lengthening of Telomeres (ALT) is an aberrant DNA recombination pathway which grants replicative immortality to approximately 10% of all cancers. Despite this high prevalence of ALT in cancer, the mechanism and genetics by which cells activate this pathway remain incompletely understood. A major challenge in dissecting the events that initiate ALT is the extremely low frequency of ALT induction in human cell systems. Guided by the genetic lesions that have been associated with ALT from cancer sequencing studies, we genetically engineered primary human pluripotent stem cells to deterministically induce ALT upon differentiation. Using this genetically defined system, we demonstrate that disruption of the p53 and Rb pathways in combination with ATRX loss-of-function is sufficient to induce all hallmarks of ALT and results in functional immortalization in a cell type-specific manner. We further demonstrate that ALT can be induced in the presence of telomerase, is neither dependent on telomere shortening nor crisis, but is rather driven by continuous telomere instability triggered by the induction of differentiation in ATRX-deficient stem cells.
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