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À propos de : Human Polynucleotide Phosphorylase Protein in Response to Oxidative Stress        

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  • Human Polynucleotide Phosphorylase Protein in Response to Oxidative Stress
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  • 8-Oxo-7,8-dihydroguanine (8-oxoGua) is generated in nucleic acids as well as in their precursorsdue to the actions of oxygen radicals produced through a normal cellular metabolism. Since oxidizedguanine can pair with both cytosine and adenine, it causes alterations in the phenotypic expression whenit is present in RNA. To prevent such an outcome, organisms must have some mechanism for eliminatingsuch oxidized guanine nucleotides from RNA and its precursors. In mammalian cells, MTH1 and NUDT5proteins degrade 8-oxoGTP and 8-oxoGDP to 8-oxoGMP, which is an unusable form for RNA synthesis.In a search for proteins functioning at the RNA level, polynucleotide phosphorylase (PNP) protein hasbeen suggested to be a good candidate for such a role. The human PNP protein has an ability to bindspecifically to RNA containing 8-oxoGua. When human cells are exposed to agents that induce oxidativestress, such as hydrogen peroxide and menadion, the amounts of PNP protein decrease rapidly whileamounts of other proteins in the cells do not change after such treatments. No specific decrease in thePNP protein level is observed when cells are treated with ACNU and cycloheximide at doses sufficientto provide the same degree of growth suppression. These results imply that the PNP protein might thusplay a role in excluding oxidized forms of RNA from the translation mechanism.
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