Home LiteratureArticle Details
PMID: 17329374 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Mechanism of the formation of DNA-protein cross-links by antitumor cisplatin.

Nucleic acids research ·Vol. 35 ·No. 6 ·2007-00-00 ·Pages 1812-21

Chválová K, Brabec V, Kaspárková J

Abstract

DNA-protein cross-links are formed by various DNA-damaging agents including antitumor platinum drugs. The natures of these ternary DNA-Pt-protein complexes (DPCLs) can be inferred, yet much remains to be learned about their structures and mechanisms of formation. We investigated the origin of these DPCLs and their cellular processing on molecular level using gel electrophoresis shift assay. We show that in cell-free media cisplatin [cis-diamminedichloridoplatinum(II)] forms DPCLs more effectively than ineffective transplatin [trans-diamminedichloridoplatinum(II)]. Mechanisms of transformation of individual types of plain DNA adducts of the platinum complexes into the DPCLs in the presence of several DNA-binding proteins have been also investigated. The DPCLs are formed by the transformation of DNA monofunctional and intrastrand cross-links of cisplatin. In contrast, interstrand cross-links of cisplatin and monofunctional adducts of transplatin are stable in presence of the proteins. The DPCLs formed by cisplatin inhibit DNA polymerization or removal of these ternary lesions from DNA by nucleotide excision repair system more effectively than plain DNA intrastrand or monofunctional adducts. Thus, the bulky DNA-protein cross-links formed by cisplatin represent a more distinct and persisting structural motif recognized by the components of downstream cellular systems processing DNA damage considerably differently than the plain DNA adducts of this metallodrug.

MeSH Terms
Antineoplastic Agents/chemistry,toxicity Cisplatin/chemistry,toxicity Cross-Linking Reagents/chemistry,toxicity DNA/biosynthesis,drug effects DNA Adducts/chemistry DNA Repair DNA-Binding Proteins/drug effects Electrophoretic Mobility Shift Assay
Chemicals
Antineoplastic Agents Cross-Linking Reagents DNA Adducts DNA-Binding Proteins cisplatin-DNA adduct transplatin DNA Cisplatin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Chválová Katerina
Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.
Brabec Viktor
Kaspárková Jana
References (38)
38 references, click to expand
  1. DNA-protein complexes induced by chromate and other carcinogens.
    Environ Health Perspect. 1991 May;92:45-52 PMID: 1935851
  2. Chemical versatility of transplatin monofunctional adducts within multiple site-specifically platinated DNA.
    Biochemistry. 1997 Jun 17;36(24):7281-7 PMID: 9200676
  3. Conversion of DNA adducts of antitumour cis-diamminedichloroplatinum(II). Immunochemical analysis.
    Eur J Pharmacol. 1992 May 12;226(1):5-13 PMID: 1397055
  4. Replication inhibition and translesion synthesis on templates containing site-specifically placed cis-diamminedichloroplatinum(II) DNA adducts.
    Biochemistry. 1992 Apr 28;31(16):3975-90 PMID: 1314653
  5. Repair of DNA-polypeptide crosslinks by human excision nuclease.
    Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4056-61 PMID: 16537484
  6. Efficient nucleotide excision repair of cisplatin, oxaliplatin, and Bis-aceto-ammine-dichloro-cyclohexylamine-platinum(IV) (JM216) platinum intrastrand DNA diadducts.
    Cancer Res. 1999 Aug 15;59(16):3968-71 PMID: 10463593
  7. Conversion of monofunctional DNA adducts of cis-diamminedichloroplatinum (II) to bifunctional lesions. Effect on the in vitro replication of single-stranded DNA by Escherichia coli DNA polymerase I and eukaryotic DNA polymerases alpha.
    J Biol Chem. 1989 Sep 5;264(25):15130-5 PMID: 2670932
  8. Recognition of cisplatin adducts by cellular proteins.
    Mutat Res. 2001 Jul 1;478(1-2):1-21 PMID: 11406166
  9. Effect of cisplatin on cell death and DNA crosslinking in rat mammary. Adenocarcinoma in vitro.
    Acta Med Okayama. 1999 Oct;53(5):201-8 PMID: 10561728
  10. Activation of trans geometry in bifunctional mononuclear platinum complexes by a piperidine ligand. Mechanistic studies on antitumor action.
    J Biol Chem. 2003 Nov 28;278(48):47516-25 PMID: 12970368
  11. Solution structure of a cisplatin-induced DNA interstrand cross-link.
    Science. 1995 Dec 15;270(5243):1842-5 PMID: 8525382
  12. Induction and repair of DNA cross-links in chinese hamster ovary cells treated with various platinum coordination compounds in relation to platinum binding to DNA, cytotoxicity, mutagenicity, and antitumor activity.
    Cancer Res. 1984 May;44(5):2043-51 PMID: 6538808
  13. DNA secondary structure effects on DNA synthesis catalyzed by HIV-1 reverse transcriptase.
    J Biol Chem. 1998 Oct 16;273(42):27259-67 PMID: 9765249
  14. Cellular processing of platinum anticancer drugs.
    Nat Rev Drug Discov. 2005 Apr;4(4):307-20 PMID: 15789122
  15. DNA modifications by antitumor platinum and ruthenium compounds: their recognition and repair.
    Prog Nucleic Acid Res Mol Biol. 2002;71:1-68 PMID: 12102553
  16. cis-Diamminedichloroplatinum(II)-induced DNA adducts in peripheral leukocytes from seven cancer patients: quantitative immunochemical detection of the adduct induction and removal after a single dose of cis-diamminedichloroplatinum(II).
    Cancer Res. 1987 Jun 1;47(11):3000-4 PMID: 3552211
  17. The major chromatin protein histone H1 binds preferentially to cis-platinum-damaged DNA.
    Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13448-51 PMID: 9391045
  18. Conformation, protein recognition and repair of DNA interstrand and intrastrand cross-links of antitumor trans-[PtCl2(NH3)(thiazole)].
    Nucleic Acids Res. 2005;33(18):5819-28 PMID: 16237123
  19. Cisplatin: from DNA damage to cancer chemotherapy.
    Prog Nucleic Acid Res Mol Biol. 2001;67:93-130 PMID: 11525387
  20. Crystal structure of a double-stranded DNA containing a cisplatin interstrand cross-link at 1.63 A resolution: hydration at the platinated site.
    Nucleic Acids Res. 1999 Apr 15;27(8):1837-46 PMID: 10101191
  21. Interaction of trans-diamminedichloroplatinum(II) with DNA: formation of monofunctional adducts and their reaction with glutathione.
    Biochemistry. 1987 Jun 16;26(12):3303-7 PMID: 3651385
  22. Trifunctional dinuclear platinum complexes as DNA-protein cross-linking agents.
    Biochemistry. 2004 Jun 22;43(24):7776-86 PMID: 15196020
  23. Recognition of major DNA adducts of enantiomeric cisplatin analogs by HMG box proteins and nucleotide excision repair of these adducts.
    Chem Biol. 2002 May;9(5):629-38 PMID: 12031669
  24. DNA-protein cross-linking in L1210 cells sensitive and resistant to cis-diamminedichloroplatinum (II).
    Mol Biol Rep. 1991 May;15(2):81-6 PMID: 1749377
  25. Structure, Recognition, and Processing of Cisplatin-DNA Adducts.
    Chem Rev. 1999 Sep 8;99(9):2467-98 PMID: 11749487
  26. Induction of DNA-protein cross-links by platinum compounds.
    Z Naturforsch C. 2000 Sep-Oct;55(9-10):731-6 PMID: 11098823
  27. DNA-protein cross-linking by trans-[PtCl(2)(E-iminoether)(2)]. A concept for activation of the trans geometry in platinum antitumor complexes.
    Nucleic Acids Res. 2003 Nov 15;31(22):6450-60 PMID: 14602903
  28. The formation, isolation and characterization of DNA adducts produced by anticancer platinum complexes.
    Pharmacol Ther. 1987;34(2):155-66 PMID: 3317449
  29. Cytotoxicity, DNA strand breakage and DNA-protein crosslinking by a novel transplatinum compound in human A2780 ovarian and MCF-7 breast carcinoma cells.
    Biochem Pharmacol. 2004 Sep 1;68(5):857-66 PMID: 15294448
  30. Single d(GpG)/cis-diammineplatinum(II) adduct-induced inhibition of DNA polymerization.
    Biochemistry. 1999 Jan 12;38(2):715-26 PMID: 9888812
  31. Interstrand cross-links are preferentially formed at the d(GC) sites in the reaction between cis-diamminedichloroplatinum (II) and DNA.
    Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1982-5 PMID: 2000402
  32. DNA-dependent transcription of adenovirus genes in a soluble whole-cell extract.
    Proc Natl Acad Sci U S A. 1980 Jul;77(7):3855-9 PMID: 6933441
  33. DNA excision repair.
    Annu Rev Biochem. 1996;65:43-81 PMID: 8811174
  34. Biophysical studies of the modification of DNA by antitumour platinum coordination complexes.
    Biophys Chem. 1990 Apr;35(2-3):129-41 PMID: 2204440
  35. Biochemical modulation of Cisplatin mechanisms of action: enhancement of antitumor activity and circumvention of drug resistance.
    Chem Rev. 2003 Mar;103(3):645-62 PMID: 12630848
  36. DNA-protein and DNA interstrand cross-linking by cis- and trans-platinum(II) diamminedichloride in L1210 mouse leukemia cells and relation to cytotoxicity.
    Cancer Res. 1979 Feb;39(2 Pt 1):365-9 PMID: 570092
  37. Immunospecific protein of 34.5 kDa from DNA-protein cross-links induced by cis- and trans-diamminedichloroplatinum.
    Cell Biol Int. 2002;26(6):495-503 PMID: 12119176
  38. In vivo DNA-protein cross-linking by cis- and trans-diamminedichloroplatinum(II).
    Cancer Res. 1987 Jan 1;47(1):201-5 PMID: 2431763
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkm032
Published
2007-00-00
Epub
2007-00-28
Pages
1812-21
Language
English
Region
England
NLM ID
0411011
PMCID
PMC1874601
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/gkm032 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2