ArticleNucleic acids research2025
ecDNA replication is disorganized and vulnerable to replication stress.
Article in Nucleic acids research, 2025. 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.
- A system-level metastable model of cancer evolution: integrating replication stress, cell cycle deregulation and chromosomal instability.Annals of medicine · 2026Review
- Article
- Extrachromosomal DNA as a platform for epigenetic reprogramming in cancer.Molecular cancer · 2026Review
- The shared evolutionary capacities of plasmids and extrachromosomal DNA.Nature reviews. Genetics · 2026Review
- Extrachromosomal DNA in urothelial carcinoma: mechanisms and clinical applications.Nature reviews. Urology · 2026Review
- RAF1 extrachromosomal DNA amplification confers acquired erlotinib resistance in a non-small cell lung cancer cell model.Signal transduction and targeted therapy · 2026Article
- Telomere-driven replicative crisis is driven by large-scale changes in genomic architecture.Genome research · 2026Article
- Replication origin flexibility: a tool to mitigate the hazards of excess replication.Trends in genetics : TIG · 2026Review
- Decoding DNA metabolism and its clinical relevance through the lens of high-throughput sequencing assays.Medical review (2021) · 2026Review
- The newfound relationship between extrachromosomal DNAs and excised signal circles.FEBS letters · 2026Review
- Integrative Transcriptomic and Machine Learning Analysis of ecDNA-Associated Features for Studying Chemotherapy Resistance in TNBC.bioRxiv : the preprint server for biology · 2026Article
- Automated mapping of DNA replication fork progression in human cells with ForkML.Nature communications · 2026Article
- Extrachromosomal DNA in Solid Tumors-Landscape, Immune Effects, and Resistance to Targeted Therapy.Oncology research · 2026Review
- Research Advances of Extrachromosomal Circular DNA in Breast Cancer.Cancer medicine · 2025Review
- Unfolding ecDNA as a pan-cancer therapeutic target.Medical review (2021) · 2025Article
- Article
- The role of extrachromosomal DNA in tumorigenesis and progression.Frontiers in oncology · 2025Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Extrachromosomal DNA (ecDNA) is a critical driver of cancer progression, contributing to tumour growth, evolution, and therapeutic resistance through oncogene amplification. Despite its significance, the replication of ecDNA remains poorly understood. In this study, we investigated the replication dynamics of ecDNA using high-resolution replication timing analysis (Repli-seq) and DNAscent, a method for measuring origin firing and replication fork movement, that we applied to both bulk DNA and to ecDNA isolated with FINE (Fluorescence-activated cell sorting-based Isolation of Native ecDNA), a new method for isolating, chromatinized ecDNA without DNA or protein digestion. We demonstrate that ecDNA in the COLO 320DM colorectal cancer cell line exhibits largely asynchronous replication throughout the S phase, contrasting with the conserved replication timing of the corresponding chromosomal DNA in RPE-1 cells and the chromosomally reintegrated ecDNA in COLO 320HSR. Replication origins on ecDNA are redistributed, and replication forks exhibit reduced velocity and increased stalling. Under replication stress induced by hydroxyurea treatment, ecDNA replication is further compromised, leading to altered origin activation, reduced fork velocity and eventual ecDNA depletion from cells. Our findings reveal fundamental differences in the replication dynamics of ecDNA, providing insights that could inform the development of therapies targeting ecDNA-associated oncogene amplification in cancer.
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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.