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Science 9 March 1979:
Vol. 203. no. 4384, pp. 1014 - 1016
DOI: 10.1126/science.370979
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Articles

Science, Vol 203, Issue 4384, 1014-1016
Copyright © 1979 by American Association for the Advancement of Science

articles

Binding of cis- and trans-dichlorodiammineplatinum(II) to DNA: evidence for unwinding and shortening of the double helix

GL Cohen, WR Bauer, JK Barton, and SJ Lippard

The antitumor drug cis-dichlorodiammineplatinum(II) (cis-DDP) and the inactive trans isomer bind and produce cooperative changes in closed and nicked circular duplex DNA's. Covalent binding of both platinum complexes to the closed circular DNA alters the degree of supercoiling, presumably by disrupting and unwinding the double helix. Electron micrographs show the platinated DNA's to be shortened by up to 50 percent of their original length. At similar ratios of bound platinum per nucleotide, the electrophoretic mobilities of the DNA's in gels containing the dye ethidium bromide are the same for both isomers. The only detectable difference in the binding of the two platinum isomers is an increase in the electrophoretic mobility in nondye gels of closed circular DNA having small amounts of bound cis-DDP that is not apparent for the trans complex.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A Ruthenium-Containing Organometallic Compound Reduces Tumor Growth through Induction of the Endoplasmic Reticulum Stress Gene CHOP.
X. Meng, M. L. Leyva, M. Jenny, I. Gross, S. Benosman, B. Fricker, S. Harlepp, P. Hebraud, A. Boos, P. Wlosik, et al. (2009)
Cancer Res. 69, 5458-5466
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cis-Diammine(pyridine)chloroplatinum(II), a monofunctional platinum(II) antitumor agent: Uptake, structure, function, and prospects.
K. S. Lovejoy, R. C. Todd, S. Zhang, M. S. McCormick, J. A. D'Aquino, J. T. Reardon, A. Sancar, K. M. Giacomini, and S. J. Lippard (2008)
PNAS 105, 8902-8907
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Reversion of Structure-Activity Relationships of Antitumor Platinum Complexes by Acetoxime but Not Hydroxylamine Ligands.
S. Zorbas-Seifried, M. A. Jakupec, N. V. Kukushkin, M. Groessl, C. G. Hartinger, O. Semenova, H. Zorbas, V. Yu. Kukushkin, and B. K. Keppler (2007)
Mol. Pharmacol. 71, 357-365
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DNA Modifications by Antitumor trans-[PtCl2(E-Iminoether)2].
R. Zaludova, Z. Balcarová, M. Coluccia, G. Natile, and V. Brabec (1997)
Mol. Pharmacol. 52, 354-361
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Mechanism of Tracking and Cleavage of Adduct-damaged DNA Substrates by the Mammalian 5'- to 3'-Exonuclease/Endonuclease RAD2 Homologue 1or Flap Endonuclease 1.
C. J. Barnes, A. F. Wahl, B. Shen, M. S. Park, and R. A. Bambara (1996)
J. Biol. Chem. 271, 29624-29631
   Abstract »    Full Text »    PDF »
Alteration of DNA Tertiary Structure by Physical and Chemical Carcinogens: Involvement in DNA Repair Processes.
S. Spadari, B. M. Sutherland, G. Pedrali-Noy, F. Focher, M. T. Chiesa, and G. Ciarrocchi (1987)
Toxicol Pathol 15, 82-87
   Abstract »    PDF »
Ethidium Bromide Alters the Binding Mode of cis-Diamminedichloroplatinum(II) to pBR322 DNA.
C.M. Merkel and S.J. Lippard (1983)
Cold Spring Harb Symp Quant Biol 47, 355-360
   Abstract »    PDF »
New chemistry of an old molecule: cis-[Pt(NH3)2Cl2].
S. Lippard (1982)
Science 218, 1075-1082
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