Informace o publikaci
Different recognition of DNA modified by antitumor cisplatin and its clinically ineffective trans isomer by tumor suppressor protein p53
| Autoři | |
|---|---|
| Rok publikování | 2001 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | Journal of Biological Chemistry |
| Fakulta / Pracoviště MU | |
| Citace | |
| Obor | Biofyzika |
| Klíčová slova | DNA; p53; protinádorová aktivita; interakce; cisplatina |
| Popis | 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. |