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Sequence-dependent termination of in vitro DNA synthesis by cis- and trans-diamminedichloroplatinum (II).
Open accessAbstract
Inhibition of DNA replication by the antitumor drug cis-diamminedichloroplatinum (II) (cis-DDP) has been proposed to be responsible for its cytotoxicity. Treatment of primed phage M13 mp8 viral DNA templates with the drug followed by second-strand synthesis using large fragment DNA polymerase I reveals that cis-DDP forms an adduct with DNA that inhibits DNA synthesis in vitro. This inhibition occurs at all (dG)n (n greater than or equal to 2) sequences in the template strand, confirming that these regions are the major cis-DDP binding sites on DNA. trans-Diamminedichloroplatinum (II), which is inactive as a drug, also forms adducts that inhibit DNA synthesis. Although considerably lower specificity is observed with the trans isomer, there appears to be a preference for d(GpNpG) sequences, where N is any intervening nucleotide. The monofunctional adduct formed between chlorodiethylenetriamineplatinum(II) chloride and DNA does not inhibit DNA synthesis in this system.
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Cited by
Marullo, R., Werner, E., Degtyareva, N., Moore, B., Altavilla, G., Ramalingam, S. S., & Doetsch, P. W. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081162 · Cited by 777
Formation and Repair of Interstrand Cross-Links in DNA
Noll, D. M., Mason, T. M., & Miller, P. S. (2006) · Chemical Reviews · doi:10.1021/cr040478b · Cited by 484
Molecular mechanisms involved in cisplatin cytotoxicity
Jordan, P., & Carmo-Fonseca*, M. (2000) · Cellular and Molecular Life Sciences · doi:10.1007/pl00000762 · Cited by 398
Metadata
- Authors
- Pinto, A. L., & Lippard, S. J.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1985-07
- Volume
- 82
- Issue
- 14
- Pages
- 4616-4619
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1987940280
- Cited by
- 219
- References
- 0
- FWCI
- 4.69
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Sequence-dependent termination of in vitro DNA synthesis by cis- and trans-diamminedichloroplatinum (II). https://app.cochat.ai/papers/10.1073/pnas.82.14.4616
- The paper
- Pinto, A. L., & Lippard, S. J. (1985). Sequence-dependent termination of in vitro DNA synthesis by cis- and trans-diamminedichloroplatinum (II). Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.82.14.4616
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
