Mécanisme d'action de la drogue anticancéreuse cis-dichlorodiammineplatine (II) : étude de l'interaction entre les protéines de réparation des mésappariements et l'ADN platiné

Abstract : The DNA mismatch repair (MMR) system is involved in mediating the cytotoxicity of the anticancer drug cisplatin that interacts with DNA. We have studied in vitro some fundamental stages of molecular mechanisms linking MMR system and cisplatin cytotoxicity. Our study investigated the interaction of MMR system MutS protein implicated in repair initiation with platinated DNA. More precisely, we are interested in : i) recognition by MutS of cisplatin cross-links and cisplatin compound lesions (with cisplatin 1,2-intrastrand cross-link on one strand and a non-complementary base opposite one of the adducted purines) ii) repair initiation modulated by the nucleotides ADP and ATP binding by MutS iii) study of a platinum compound (DACH-platin) having no cross-resistance with cisplatin. Main results obtained by electrophoretic and surface plasmon resonance techniques show the ability of MutS to sense differentially various platinated DNA substrates and that platinated DNA may play a cofactor role in the biochemical regulation of MutS activity in presence of nucleotides. Our results suggest that cisplatin major intrastrand 1,2-d(GpG) compound lesions are probably critical in determining MMR-mediated cisplatin cytotoxicity.
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https://tel.archives-ouvertes.fr/tel-00483029
Contributor : Laurence Fourrier-Bauchet <>
Submitted on : Wednesday, May 12, 2010 - 1:00:44 PM
Last modification on : Wednesday, June 27, 2018 - 8:24:02 AM
Long-term archiving on : Thursday, September 16, 2010 - 2:33:44 PM

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  • HAL Id : tel-00483029, version 1

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Laurence Fourrier-Bauchet. Mécanisme d'action de la drogue anticancéreuse cis-dichlorodiammineplatine (II) : étude de l'interaction entre les protéines de réparation des mésappariements et l'ADN platiné. Biochimie [q-bio.BM]. Université d'Orléans, 2003. Français. ⟨tel-00483029⟩

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