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DNA sequence selectivity of human topoisomerase I‐mediated DNA cleavage induced by camptothecin
Open accessAbstract
In probing the mechanism of inhibition of hypoxia inducible factor (HIF‐1) by campothecins, we investigated the ability of human topoisomerase I to bind and cleave HIF‐1 response element (HRE), which contains the known camptothecin‐mediated topoisomerase I cleavage site 5′‐TG. We observed that the selection of 5′‐TG by human topoisomerase I and topotecan depends to a large extent on the specific flanking sequences, and that the presence of a G at the −2 position (where cleavage occurs between −1 and +1) prevents the HRE site from being a preferred site for such cleavage. Furthermore, the presence of −2 T/A can induce the cleavage at a less preferred TC or TA site. However, in the absence of a more preferred site, the HRE site is shown to be cleaved by human topoisomerase I in the presence of topotecan. Thus, it is implied that the −2 base has a significant influence on the selection of the camptothecin‐mediated Topo I cleavage site, which can overcome the preference for +1G. While the cleavage site recognition has been known to be based on the concerted effect of several bases spanning the cleavage site, such a determining effect of an individual base has not been previously recognized. A possible base‐specific interaction between DNA and topoisomerase I may be responsible for this sequence selectivity.
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“Accordingly, this model rationalizes the selective suppression of only a fraction of the HIF transcriptional program and suggests that gene-specific sensitivity to topoisomerase inhibitors may depend on local DNA sequence context.”
From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [323]
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“Camptothecin-mediated stabilization of TopI cleavage complexes at or near HREs may therefore interfere with HIF-1 binding to its target DNA sequences [323].”
From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [323]
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“Although HREs are not canonical TopI cleavage sites, they may become functional targets in the absence of higher-affinity sequences [323].”
From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [323]
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“The consensus hypoxia response element (5′-RCGTG-3′) contains the dinucleotide 5′-TG, which is frequently observed at camptothecin-stabilized TopI cleavage sites.”
From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [323]
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Research works printed but not linked: 22
- 10.1016/S0021-9258(17)38654-4 · DOI · Paper page
- Hsiang YH, 1988, Identification of mammalian DNA topoisomerase I as an intracellular target of the anticancer drug camptothecin, Cancer Res, 48, 1722
- 10.1073/pnas.242259599 · DOI
- Rapisarda A, 2002, Identification of small molecule inhibitors of hypoxia‐inducible factor 1 transcriptional activation pathway, Cancer Res, 62, 4316
- 10.1158/0008-5472.CAN-03-3139 · DOI · Paper page
- 10.1016/0167-4781(84)90066-6 · DOI
- 10.1016/0022-2836(88)90462-7 · DOI
- 10.1128/MCB.9.2.541 · DOI
- Jaxel C, 1991, Effect of local DNA sequence on topoisomerase I cleavage in the presence or absence of camptothecin, J Biol Chem, 266, 20418, 10.1016/S0021-9258(18)54939-5 · DOI
- 10.1093/nar/21.22.5157 · DOI
- 10.1021/bi00021a035 · DOI
- 10.1093/nar/16.23.11157 · DOI
- 10.1093/nar/17.21.8521 · DOI
- 10.1016/S0092-8674(85)80027-1 · DOI
- Valenti M, 1997, Novel 7‐alkyl methylenedioxy‐camptothecin derivatives exhibit increased cytotoxicity and induce persistent cleavable complexes both with purified mammalian topoisomerase I and in human colon carcinoma SW620 cells, Mol Pharmacol, 52, 82, 10.1124/mol.52.1.82 · DOI
- 10.1016/S0076-6879(01)40445-9 · DOI
- 10.1093/nar/25.20.4111 · DOI
- 10.1126/science.279.5356.1504 · DOI
- 10.1126/science.279.5356.1534 · DOI
- 10.1021/bi992690t · DOI
- 10.1074/jbc.M309959200 · DOI
- Stewart L, 1997, Purification of baculovirus‐expressed human DNA topoisomerase I, Methods Mol Biol, 94, 223
Cited by
Sorted by citations
HIF inhibition: Current strategies and clinical challenges
Więch-Walów, A., Bartoszewska, S., Barton, A., Czechowicz, P., Dudzik, J., Wielockx, B., Collawn, J. F., & Bartoszewski, R. (2026) · Redox biology · doi:10.1016/j.redox.2026.104220 · Cited by 3
“Although HREs are not canonical TopI cleavage sites, they may become functional targets in the absence of higher-affinity sequences [323].”
Metadata
- Authors
- Punchihewa, C., Carver, M., & Yang, D.
- Affiliations
- University of Arizona (US)
- Corresponding author
- Yang, Danzhou
- Venue
- Protein Science
- Publisher
- Wiley
- Published
- 2009-05-26
- Volume
- 18
- Issue
- 6
- Pages
- 1326-1331
- ISSN
- 0961-8368 (ISSN-L)
- 1469-896X
- PMC
- PMC2774443
- OpenAlex
- W2113957888
- Cited by
- 3
- References
- 0
- Citations by year
- 2026: 1 · 2024: 2
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Protein Science (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01CA122952, K01CA083886)
- National Center for Research Resources (S10RR016659)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer therapeutics and mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
- Keywords
- topoisomerase I, camptothecin, topotecan, hypoxia-inducible factor, DNA binding, topoisomerase I inhibition
- MeSH terms
- Base Sequence, Camptothecin, DNA Topoisomerases, Type I, Enzyme Inhibitors, Humans, Oligonucleotides, Recombinant Proteins, Response Elements, Hypoxia-Inducible Factor 1, DNA Cleavage, Topoisomerase I Inhibitors
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