ArticleProceedings of the National Academy of Sciences of the United States of America2011
Hydroxyurea induces de novo copy number variants in human cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 100 citations in OpenAlex.
- Replication stress increases de novo CNVs across the malaria parasite genome.Nucleic acids research · 2026Article
- When Blood Disorders Meet Cancer: Uncovering the Oncogenic Landscape of Sickle Cell Disease.Journal of clinical medicine · 2025Review
- Origin of chromosome 12 trisomy surge in human induced pluripotent stem cells.The Journal of cell biology · 2025Article
- Replication stress increases de novo CNVs across the malaria parasite genome.bioRxiv : the preprint server for biology · 2025Article
- DNA glycosylase (NEIL3) overexpression associated with low tumor immune infiltration and poor overall patient survival in endometrial cancer.Scientific reports · 2025Article
- Myeloproliferative Neoplasms: Challenging Dogma.Journal of clinical medicine · 2024Review
- Replication stress induces POLQ-mediated structural variant formation throughout common fragile sites after entry into mitosis.Nature communications · 2024Article
- The loci of environmental adaptation in a model eukaryote.Nature communications · 2024Article
- CK2-dependent degradation of CBX3 dictates replication fork stalling and PARP inhibitor sensitivity.Science advances · 2024Article
- Copy Number Variations in Pancreatic Cancer: From Biological Significance to Clinical Utility.International journal of molecular sciences · 2023Review
- Mistimed origin licensing and activation stabilize common fragile sites under tight DNA-replication checkpoint activation.Nature structural & molecular biology · 2023Article
- Replication stress generates distinctive landscapes of DNA copy number alterations and chromosome scale losses.Genome biology · 2022Article
- Copy Number Alterations as Novel Biomarkers and Therapeutic Targets in Colorectal Cancer.Cancers · 2022Review
- Stimulation of adaptive gene amplification by origin firing under replication fork constraint.Nucleic acids research · 2022Article
- Locus-specific transcription silencing at the FHIT gene suppresses replication stress-induced copy number variant formation and associated replication delay.Nucleic acids research · 2021Article
- Hydroxyurea Induces a Stress Response That Alters DNA Replication and Nucleotide Metabolism in Bacillus subtilis.Journal of bacteriology · 2021Article
- Double-strand breaks induce short-scale DNA replication and damage amplification in the fully grown mouse oocytes.Genetics · 2021Article
- Therapeutic Dose of Hydroxyurea-Induced Synaptic Abnormalities on the Mouse Spermatocyte.Frontiers in physiology · 2021Article
- Somatic Copy Number Alterations in Human Cancers: An Analysis of Publicly Available Data From The Cancer Genome Atlas.Frontiers in oncology · 2021Article
- An evolving view of copy number variants.Current genetics · 2019Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Copy number variants (CNVs) are widely distributed throughout the human genome, where they contribute to genetic variation and phenotypic diversity. Spontaneous CNVs are also a major cause of genetic and developmental disorders and arise frequently in cancer cells. As with all mutation classes, genetic and environmental factors almost certainly increase the risk for new and deleterious CNVs. However, despite the importance of CNVs, there is limited understanding of these precipitating risk factors and the mechanisms responsible for a large percentage of CNVs. Here we report that low doses of hydroxyurea, an inhibitor of ribonucleotide reductase and an important drug in the treatment of sickle cell disease and other diseases induces a high frequency of de novo CNVs in cultured human cells that resemble pathogenic and aphidicolin-induced CNVs in size and breakpoint structure. These CNVs are distributed throughout the genome, with some hotspots of de novo CNV formation. Sequencing revealed that CNV breakpoint junctions are characterized by short microhomologies, blunt ends, and short insertions. These data provide direct experimental support for models of replication-error origins of CNVs and suggest that any agent or condition that leads to replication stress has the potential to induce deleterious CNVs. In addition, they point to a need for further study of the genomic consequences of the therapeutic use of hydroxyurea.
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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.