Use of short duplexes for the analysis of the sequence-dependent cleavage of DNA by a chemical nuclease, a manganese porphyrin.
A manganese porphyrin, manganese(III)-bis(aqua)-meso-tetrakis(4-N-methylpyridiniumyl)porphyrin, in the presence of KHSO5 is able to perform deoxyribose or guanine oxidation depending on its mode of interaction with DNA. These two reactions involve an oxygen-atom transfer or an electron transfer, respectively. The oxidative reactivity of the manganese-oxo porphyrin was compared on short oligonucleotide duplexes of different sequences. The major mechanism of DNA damage is due to deoxyribose hydroxylation at a site of strong interaction, an (A.T)3 sequence. Guanine oxidation by electron transfer was found not to be competitive with this major mechanism. It was found that a single intrastrand guanine was three orders of magnitude less reactive than an (A.T)3 sequence. The reactivity of a 5'-GG sequence was found to be intermediate and was estimated to be two orders of magnitude less than that of an (A.T)3 site. Short oligonucleotide duplexes, as double-stranded-DNA models, proved to be convenient tools for the study of the comparative reactivity of this reagent toward different sequences of DNA. However, they showed a particular reactivity at their terminal base pairs (the "end effect") that biased their modeling capacity for double-helix-DNA models.
Mourgues
Sophie
S
Laboratoire de Chimie de Coordination du CNRS, 205, route de Narbonne, 31077 Toulouse Cedex 4, France.
Kupan
Adam
A
Pratviel
Geneviève
G
Meunier
Bernard
B
D001483:Base Sequence; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D006147:Guanine / Q000378:metabolism; D008345:Manganese; D009841:Oligonucleotides / Q000378:metabolism*; D010084:Oxidation-Reduction; D011166:Porphyrins / Q000494:pharmacology*
D009841:Oligonucleotides; D011166:Porphyrins; D008345:Manganese; D006147:Guanine; D004247:DNA