ArticleNucleic acids research2023
Induction of the alternative lengthening of telomeres pathway by trapping of proteins on DNA.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- Twisting the End Game: How Telomere Chromatin Modifications Shape Telomere Maintenance.Aging cell · 2026Review
- G-quadruplex homeostasis is a determinant of PARP inhibitor toxicity in BRCA2-deficient cells.Nature communications · 2026Article
- Structural organization and function of telomeric chromatin.Nature cell biology · 2026Review
- The cGAS-STING pathway in fibroblast microenvironment: from molecular mechanisms to targeted therapies.Apoptosis : an international journal on programmed cell death · 2026Review
- ATRX safeguards cellular identity duringbioRxiv : the preprint server for biology · 2026Article
- The alternative lengthening of telomeres pathway through a DNA repair lens: mechanism and therapeutic opportunities.NAR cancer · 2025Review
- Silencing of SOD1 sensitises ATRX-deficient cells to camptothecin treatment through increased activity of the alternative lengthening of telomeres pathway.Human molecular genetics · 2025Article
- Poly (ADP-ribose) polymerase in yeasts: characterization and involvement in telomere maintenance.Nucleic acids research · 2025Article
- Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity.Biogerontology · 2025Article
- Topoisomerase IIIα controls alternative lengthening of telomeres.Cell reports · 2025Article
- Atypical R-loops in cancer: decoding molecular chaos for therapeutic gain.Journal of translational medicine · 2025Review
- Cellular adaptations impact the biological activity of naphthalene diimide G-quadruplex ligands in ALT-positive osteosarcoma cells.Cell death & disease · 2025Article
- Multi-omics analysis reveals the panoramic picture of TOP2A in pan-cancer.Scientific reports · 2025Article
- Locking the gates of immortality: targeting alternative lengthening of telomeres (ALT) pathways.Medical oncology (Northwood, London, England) · 2025Review
- Elevated reactive oxygen species can drive the alternative lengthening of telomeres pathway in ATRX-null cancers.Nucleic acids research · 2025Article
- TERRA and the alternative lengthening of telomeres: a dangerous affair.FEBS letters · 2025Review
- Phosphorylation of 'SDT-like' motifs in ATRX mediates its interaction with the MRN complex and is important for ALT pathway suppression.Open biology · 2024Article
- A First-in-Class High-Throughput Screen to Discover Modulators of the Alternative Lengthening of Telomeres (ALT) Pathway.ACS pharmacology & translational science · 2024Article
- Orphan nuclear receptors-induced ALT-associated PML bodies are targets for ALT inhibition.Nucleic acids research · 2024Article
- Oxidative guanine base damage plays a dual role in regulating productive ALT-associated homology-directed repair.Cell reports · 2024Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Telomere maintenance is a hallmark of malignant cells and allows cancers to divide indefinitely. In some cancers, this is achieved through the alternative lengthening of telomeres (ALT) pathway. Whilst loss of ATRX is a near universal feature of ALT-cancers, it is insufficient in isolation. As such, other cellular events must be necessary - but the exact nature of the secondary events has remained elusive. Here, we report that trapping of proteins (such as TOP1, TOP2A and PARP1) on DNA leads to ALT induction in cells lacking ATRX. We demonstrate that protein-trapping chemotherapeutic agents, such as etoposide, camptothecin and talazoparib, induce ALT markers specifically in ATRX-null cells. Further, we show that treatment with G4-stabilising drugs cause an increase in trapped TOP2A levels which leads to ALT induction in ATRX-null cells. This process is MUS81-endonuclease and break-induced replication dependent, suggesting that protein trapping leads to replication fork stalling, with these forks being aberrantly processed in the absence of ATRX. Finally, we show ALT-positive cells harbour a higher load of genome-wide trapped proteins, such as TOP1, and knockdown of TOP1 reduced ALT activity. Taken together, these findings suggest that protein trapping is a fundamental driving force behind ALT-biology in ATRX-deficient malignancies.
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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.