The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
Conversion of Topoisomerase I Cleavage Complexes on the Leading Strand of Ribosomal DNA into 5′-Phosphorylated DNA Double-Strand Breaks by Replication Runoff
Open accessAbstract
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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Cites
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Molecular Mechanisms of Ultraviolet Radiation‐Induced DNA Damage and Repair
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Self-citation
Metadata
- Authors
- Strumberg, D., Pilon, A. A., Smith, M., Hickey, R., Malkas, L., & Pommier, Y.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2000-06-01
- Volume
- 20
- Issue
- 11
- Pages
- 3977-3987
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2158699530
- Cited by
- 367
- References
- 59
- FWCI
- 4.51
- Type
- journal article
- Language
- en
- Open access
- green
- Licence
- journals.asm.org/non-commercial-tdm-license (tdm)
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- Strumberg, D., Pilon, A. A., Smith, M., Hickey, R., Malkas, L., & Pommier, Y. (2000). Conversion of Topoisomerase I Cleavage Complexes on the Leading Strand of Ribosomal DNA into 5′-Phosphorylated DNA Double-Strand Breaks by Replication Runoff. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.20.11.3977-3987.2000
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