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Specific Binding of Chromosomal Protein HMG1 to DNA Damaged by the Anticancer Drug Cisplatin
Abstract
The mechanism of action of the anticancer compound cis -diamminedichloroplatinum(II) (cisplatin) involves covalent binding to DNA. In an effort to understand the tumor-specific cytotoxicity of such DNA damage, the interactions of these lesions with cellular proteins have been studied. One such protein has been identified as the high-mobility group protein HMG1. Recombinant rat HMG1 binds specifically (dissociation constant 3.7 ± 2.0 × 10 -7 molar) to DNA containing cisplatin d(GpG) or d(ApG) intrastrand cross-links, which unwind and bend DNA in a specific manner, but not to DNA modified by therapeutically inactive platinum analogs. These results suggest how HMG1 might bind to altered DNA structures and may be helpful in designing new antitumor drugs.
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Cited by
Kang, R., Chen, R., Zhang, Q., Hou, W., Wu, S., Cao, L., Huang, J., Yu, Y., Fan, X.-G., Yan, Z., et al. (2014) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2014.05.001 · Cited by 956
Structural basis for DNA bending by the architectural transcription factor LEF-1
Love, J. J., Li, X., Case, D. A., Giese, K., Grosschedl, R., & Wright, P. E. (1995) · Nature · doi:10.1038/376791a0 · Cited by 573
Mechanisms of DNA Excision Repair
Sancar, A. (1994) · Science · doi:10.1126/science.7801120 · Cited by 555
SRY, like HMG1, recognizes sharp angles in DNA.
Ferrari, S., Harley, V. R., Pontiggia, A., Goodfellow, P. N., Lovell-Badge, R., & Bianchi, M. E. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05551.x · Cited by 441
Gadd45, a p53-Responsive Stress Protein, Modifies DNA Accessibility on Damaged Chromatin
Carrier, F., Georgel, P. T., Pourquier, P., Blake, M., Kontny, H. U., Antinore, M. J., Gariboldi, M., Myers, T. G., Weinstein, J. N., Pommier, Y., et al. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.3.1673 · Cited by 277
Metadata
- Authors
- Pil, P. M., & Lippard, S. J.
- Venue
- Science
- Published
- 1992-04-10
- Volume
- 256
- Issue
- 5054
- Pages
- 234-237
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2090995659
- Cited by
- 496
- References
- 0
- FWCI
- 16.39
- Type
- journal article
- Language
- en
- Open access
- closed
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- Pil, P. M., & Lippard, S. J. (1992). Specific Binding of Chromosomal Protein HMG1 to DNA Damaged by the Anticancer Drug Cisplatin. Science. https://doi.org/10.1126/science.1566071
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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.
