KAŠPÁRKOVÁ, Jana, Šárka POSPÍŠILOVÁ and Viktor BRABEC. Different recognition of DNA modified by antitumor cisplatin and its clinically ineffective trans isomer by tumor suppressor protein p53. Journal of Biological Chemistry. Bethesda, USA: Amer. Soc. Biochem. Mol., 2001, vol. 276, No 19, p. 16064-16069. ISSN 0021-9258.
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Basic information
Original name Different recognition of DNA modified by antitumor cisplatin and its clinically ineffective trans isomer by tumor suppressor protein p53
Authors KAŠPÁRKOVÁ, Jana, Šárka POSPÍŠILOVÁ and Viktor BRABEC.
Edition Journal of Biological Chemistry, Bethesda, USA, Amer. Soc. Biochem. Mol. 2001, 0021-9258.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10610 Biophysics
Country of publisher Czech Republic
Confidentiality degree is not subject to a state or trade secret
Impact factor Impact factor: 7.258
RIV identification code RIV/00216224:14310/01:00004213
Organization unit Faculty of Science
Keywords in English DNA; p53; protinádorová aktivita; interakce; cisplatina
Tags cisplatina, DNA, interakce, p53, protinádorová aktivita
Changed by Changed by: prof. RNDr. Viktor Brabec, DrSc., učo 46787. Changed: 25/5/2001 15:16.
Abstract
DNA binding activity of p53 protein is crucial for its tumor suppressor function. DNA interactions of active wild-type human p53 protein with DNA fragments and oligodeoxyribonucleotide duplexes modified by antitumor cisplatin and its clinically ineffective trans isomer (transplatin) was investigated by using gel-mobility-shift assay. It was found that DNA adducts of cisplatin reduced binding affinity of the consensus DNA sequence to p53 whereas transplatin adducts do not. This result was interpreted to mean that the precise steric fit required for formation and stability of the tetrameric complex of p53 with the consensus sequence cannot be attained as a consequence of severe conformational perturbances induced in DNA by cisplatin adducts. The results also demonstrate an increase of the binding affinity of p53 to DNA lacking the consensus sequence and modified by cisplatin, but not by transplatin.
Links
GA305/99/0695, research and development projectName: Ovlivnění konformace DNA protinádorově účinnými komplexy kovů. Vztah k vývoji nových cytostatik.
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