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Recognition and repair of DNA-cisplatin adducts.

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Woźniak K., Błasiak J.
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vol. 49
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issue 3
583-596
EN
Anticancer activity of cisplatin (cis-diamminedichloroplatinum) is believed to result from its interaction with DNA. The drug reacts with nucleophilic sites in DNA forming monoadducts as well as intra- and interstrand crosslinks. DNA-cisplatin adducts are specifically recognized by several proteins. They can be divided into two classes. One constitutes proteins which recognize DNA damage as an initial step of the nucleotide excision and mismatch repair pathways. The other class contains proteins stabilizing cellular DNA-protein and protein-protein complexes, including non-histone proteins from the HMG (high-mobility-group) family. They specifically recognize 1,2-interstrand d(GpG) and d(ApG) crosslinks of DNA-cisplatin adducts and inhibit their repair. Many HMG-domain proteins can function as transcription factors, e.g. UBF, an RNA polymerase I transcription factor, the mammalian testis-determining factor SRY and the human mitochondrial transcription factor mtTFA. Moreover, it seems that some proteins, which probably recognize DNA-cisplatin adducts non-specifically, e.g. actin and other nuclear matrix proteins, can disturb the structural and functional organization of the nucleus and whole cell. The formation of complexes between DNA and proteins in the presence of cisplatin and the changes in the cell architecture may account for the drug cytotoxicity.
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Electrophoretic analysis of DNA-actin links induced by cis- and trans-diamminedichloroplatinum (II)

81%
Walter Z., Woźniak K., Kaźmierczyk M., University of Łódź D. o. M. G.
Acta Universitatis Lodziensis. Folia Biochimica et Biophysica
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1997
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vol. 12
PL
Celem pracy jest zbadanie wpływu związków platyny: cis- i trans-diamminodichloroplatyny (II) na interakcję DNA i aktyny in vitro. W doświadczeniu wykorzystano DNA wyizolowany z leukocytów wieprzowej krwi obwodowej oraz aktynę firmy SIGMA. Badania były prowadzone metodą analizy elektroforetycznej. Stwierdzono zmniejszenie ruchliwości elektroforetycznej DNA po inkubacji z cis- i trans-diamminodichloroplatyną (II) przy rt równym 0,5, 1, 2. W przypadku prób inkubacyjnych zawierających cis-diamminodichloroplatynę i aktynę stwierdzono zmniejszenie ruchliwości elektroforetycznej DNA. Elektrotransfer aktyny uwidocznił zmniejszenie ruchliwości elektroforetycznej białka w próbach inkubacyjnych zawierających cis-diamminodichloroplatynę. Obserwacje te świadczą o wytworzeniu wiązań krzyżowych DNA-aktyna przez cis-diamminodichloroplatynę.
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