ArticleNucleic acids research2008
Mechanistic studies on bleomycin-mediated DNA damage: multiple binding modes can result in double-stranded DNA cleavage.
Article in Nucleic acids research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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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.
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Who cites it
83 citing papers in PubMed, 150 citations in OpenAlex.
- DNA damage response associated miRNA dysregulation in Ataxia-telangiectasia.Molecular biology reports · 2026Article
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- Centromeric α-satellite DNA is a hotspot of genotoxic damage, incomplete repair, and cytoplasmic mislocalization.bioRxiv : the preprint server for biology · 2026Article
- Polypharmacology in malaria treatment: single drugs, multiple mechanisms, greater impact.Trends in parasitology · 2026Review
- Combined Therapy with Pirfenidone, Metformin, and Mesenchymal Stem Cells Attenuates Bleomycin-Induced Pulmonary Fibrosis in Rats.Biomedicines · 2026Article
- Modulatory effects of CeOParticle and fibre toxicology · 2026Article
- The use of a bipolar single-needle electrode for electrochemotherapy combined with gene electrotransfer of IL-12 in a mast cell tumor on the nasal planum of a dog: case report.Frontiers in veterinary science · 2026Article
- Effect of Bleomycin Hydrolase Expression in Tumor Tissue on the Therapeutic Effectiveness of Electrochemotherapy.Cancers · 2025Article
- Centromere Instability Drives Chromosome Damage and Autoantigen Exposure in Systemic Sclerosis.bioRxiv : the preprint server for biology · 2025Article
- Fmp45 promotes Rad53 dephosphorylation via Ptc2 interaction to attenuate checkpoint signaling and maintain genome stability.Journal, genetic engineering & biotechnology · 2025Article
- Biophysical and biological properties of splice-switching oligonucleotides and click conjugates containing LNA-phosphothiotriester linkages.Nucleic acids research · 2025Article
- Influence of pH and lysis duration on DNA damage detection: a comparison of neutral and alkaline comet assays.Mutagenesis · 2025Article
- The E3 ubiquitin ligase DTX3L and the deubiquitinase USP28 fine-tune DNA repair through mutual regulation of their protein levels.iScience · 2025Article
- Synthesis, anticancer evaluation, and electrochemical investigation of new chiral pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulfonamides.Scientific reports · 2025Article
- Targeting the TGF-β-p21 axis: a critical regulator of bleomycin-induced cell cycle arrest and apoptosis in vitro-implication for progressive cervical cancer therapy.Medical oncology (Northwood, London, England) · 2025Article
- Pathogen-encoded Rum DNA polymerase drives rapid bacterial drug resistance.Nucleic acids research · 2024Article
- Amodiaquine ameliorates stress-induced premature cellular senescence via promoting SIRT1-mediated HR repair.Cell death discovery · 2024Article
- Screen-Printed Electrodes-A Promising Tool for Antineoplastic Drug Detection (Cisplatin and Bleomycin) in Biological Samples.International journal of molecular sciences · 2024Article
- High-efficiency transgene integration by homology-directed repair in human primary cells using DNA-PKcs inhibition.Nature biotechnology · 2024Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The bleomycins (BLMs) are a family of natural glycopeptides used clinically as antitumor agents. In the presence of required cofactors (Fe(2+) and O(2)), BLM causes both single-stranded (ss) and double-stranded (ds) DNA damage with the latter thought to be the major source of cytotoxicity. Previous biochemical and structural studies have demonstrated that BLM can mediate ss cleavage through multiple binding modes. However, our studies have suggested that ds cleavage occurs by partial intercalation of BLM's bithiazole tail 3' to the first cleavage site that facilitates its re-activation and re-organization to the second strand without dissociation from the DNA where the second cleavage event occurs. To test this model, a BLM A5 analog (CD-BLM) with beta-cyclodextrin attached to its terminal amine was synthesized. This attachment presumably precludes binding via intercalation. Cleavage studies measuring ss:ds ratios by two independent methods were carried out. Studies using [(32)P]-hairpin technology harboring a single ds cleavage site reveal a ss:ds ratio of 6.7 +/- 1.2:1 for CD-BLM and 3.4:1 and 3.1 +/- 0.3:1 for BLM A2 and A5, respectively. In contrast with BLM A5 and A2, however, CD-BLM mediates ds-DNA cleavage through cooperative binding of a second CD-BLM molecule to effect cleavage on the second strand. Studies using the supercoiled plasmid relaxation assay revealed a ss:ds ratio of 2.8:1 for CD-BLM in comparison with 7.3:1 and 5.8:1, for BLM A2 and A5, respectively. This result in conjunction with the hairpin results suggest that multiple binding modes of a single BLM can lead to ds-DNA cleavage and that ds cleavage can occur using one or two BLM molecules. The significance of the current study to understanding BLM's action in vivo is discussed.
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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.