ArticleMolecular and cellular biology2000
Conversion of topoisomerase I cleavage complexes on the leading strand of ribosomal DNA into 5'-phosphorylated DNA double-strand breaks by replication runoff.
Article in Molecular and cellular biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 180 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
180 citing papers in PubMed, 354 citations in OpenAlex.
- Patient-derived separation-of-function mutations reveal specific role for BRCA1 coiled coil domain in genome stability.Nature communications · 2026Article
- Molecular Determinants of Response and Rational Drug Combinations for Antibody-Drug Conjugates (ADCs) with Topoisomerase I (TOP1) Inhibitor Payloads.Journal of molecular biology · 2026Review
- Replication stress induced exposure to methotrexate in root meristem cells of Vicia faba.Histochemistry and cell biology · 2026Article
- Distinct repair outcomes from single and convergent replication fork collapse.Nature structural & molecular biology · 2026Article
- Topoisomerase I inhibitor antibody-drug conjugates in breast cancer: the relevance of the DNA damage response to resistance, response, and combination treatment strategies.Breast cancer research and treatment · 2026Review
- Slx4 and Fun30/SMARCAD1 coordinate S-phase checkpoint regulation and replication fork protection in response to Top1-DNA crosslinks.Nucleic acids research · 2026Article
- Topoisomerase I Inhibition in ETV4-overexpressed Non-Small Cell Lung Cancer Promotes Replication and Transcription Mediated R-Loop Accumulation and DNA Damage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Pathogenic variants in MAEA disrupt DNA replication fork stability and are associated with developmental abnormalities in humans.Science advances · 2025Article
- Selective targeting of genome amplifications and repeat elements by CRISPR-Cas9 nickases to promote cancer cell death.Nature communications · 2025Article
- Oxidative damage to DNA, expression of Mt-1, and activation of repair mechanisms induced by vanadium trioxide in cultures of human lymphocytes.Toxicology reports · 2025Article
- Causes and consequences of DNA double-stranded breaks in cardiovascular disease.Molecular and cellular biochemistry · 2025Review
- A Rfa1-MN-based system reveals new factors involved in the rescue of broken replication forks.PLoS genetics · 2025Article
- Flap endonuclease 1 repairs DNA-protein cross-links via ADP-ribosylation-dependent mechanisms.Science advances · 2025Article
- Two-ended recombination at a Flp-nickase-broken replication fork.Molecular cell · 2025Article
- DNA nicks in both leading and lagging strand templates can trigger break-induced replication.Molecular cell · 2025Article
- Use of Xenopus Egg Extracts to Study the Effects of Topoisomerase Poisons During Vertebrate DNA Replication.Methods in molecular biology (Clifton, N.J.) · 2025Article
- One-ended and two-ended breaks at nickase-broken replication forks.DNA repair · 2024Review
- Review
- Mechanisms controlling replication fork stalling and collapse at topoisomerase 1 cleavage complexes.Molecular cell · 2024Article
- Detection of DNA Breaks in Dividing Human Cells by Neutral Comet Assay.Journal of visualized experiments : JoVE · 2024Article
120 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Topoisomerase I cleavage complexes can be induced by a variety of DNA damages and by the anticancer drug camptothecin. We have developed a ligation-mediated PCR (LM-PCR) assay to analyze replication-mediated DNA double-strand breaks induced by topoisomerase I cleavage complexes in human colon carcinoma HT29 cells at the nucleotide level. We found that conversion of topoisomerase I cleavage complexes into replication-mediated DNA double-strand breaks was only detectable on the leading strand for DNA synthesis, which suggests an asymmetry in the way that topoisomerase I cleavage complexes are metabolized on the two arms of a replication fork. Extension by Taq DNA polymerase was not required for ligation to the LM-PCR primer, indicating that the 3' DNA ends are extended by DNA polymerase in vivo closely to the 5' ends of the topoisomerase I cleavage complexes. These findings suggest that the replication-mediated DNA double-strand breaks generated at topoisomerase I cleavage sites are produced by replication runoff. We also found that the 5' ends of these DNA double-strand breaks are phosphorylated in vivo, which suggests that a DNA 5' kinase activity acts on the double-strand ends generated by replication runoff. The replication-mediated DNA double-strand breaks were rapidly reversible after cessation of the topoisomerase I cleavage complexes, suggesting the existence of efficient repair pathways for removal of topoisomerase I-DNA covalent adducts in ribosomal DNA.
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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.