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Détection, caractérisation et mesure d'un nouveau dommage radio-induit de l'ADN isolé et cellulaire

Peggy Regulus 1
1 LAN - Laboratoire Lésions des Acides Nucléiques
SCIB - UMR E3 - Service de Chimie Inorganique et Biologique : DSM/INAC/SCIB
Abstract : Deoxyribonucleic acid (DNA) contains the genetic information and chemical injury to this macromolecule may have severe biological consequences. We report here the detection of 4 new radiation-induced DNA lesions by using a high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) approach. For that purpose, the characteristic fragmentation of most 2'-deoxyribonucleosides, the loss of 116 Da corresponding to the loss of the 2-deoxyribose moiety, was used in the so-called neutral loss mode of the HPLC-MS/MS. One of the newly detected lesions, named dCyd341 because it is a 2'-deoxycytidine modification exhibiting a molecular weight of 341 Da, was also detected in cellular DNA. Characterization of this modified nucleoside was performed using NMR and exact mass determination of the product obtained by chemical synthesis. A mechanism of formation was then proposed, in which the first event is the H-abstraction at the C4 position of a 2-deoxyribose moiety. Then, the sugar modification produced exhibits a reactive aldehyde that, through reaction with a vicinal cytosine base, gives rise to dCyd341. dCyd341 could be considered as a complex damage since its formation involves a DNA strand break and a cross-link between a damaged sugar residue and a vicinal cytosine base located most probably on the complementary DNA strand. In addition to its characterization, preliminary biological studies revealed that cells are able to remove the lesion from DNA.
Repair studies have revealed the ability of cells to excise the lesion. Identification of the repair systems involved could represent an interesting challenge.
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Peggy Regulus. Détection, caractérisation et mesure d'un nouveau dommage radio-induit de l'ADN isolé et cellulaire. Sciences du Vivant [q-bio]. Université Joseph-Fourier - Grenoble I, 2006. Français. ⟨tel-00134380⟩

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