Oxidized purine nucleotides, genome instability and neurodegeneration

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• 作者：Ilenia Ventura ; Maria Teresa Russo ; Gabriele De Luca ; Margherita Bignami
• 关键词：Neurodegenerative disease ; 8-Oxo-dGTP ; MTH1 ; Genome instability ; Oxidative DNA damage ; Trinucleotide expansion
• 刊名：Mutation Research/Genetic Toxicology and Environmental Mutagenesis
• 出版年：2010
• 出版时间：28 November 2010
• 年：2010
• 卷：703
• 期：1
• 页码：59-65
• 全文大小：464 K

文摘

Oxidative DNA damage can be the consequence of endogenous metabolic processes and exogenous insults and several DNA repair enzymes provide protection against the toxic effects of oxidized DNA bases. Here we review the increasing knowledge on the relationship between an oxidized dNTPs pool and genome instability. The review also describes some important progress toward understanding the role of oxidative DNA damage and its repair in neurodegenerative diseases. In particular the hMTH1 hydrolase destroys oxidized nucleic acid precursors to prevent their harmful incorporation into DNA and RNA. Based on results obtained in our transgenic mouse overexpressing hMTH1 in the brain we discussed the mechanisms by which this hydrolase protects against neurodegeneration in Huntington disease models.