Pathways controlling dNTP pools to maintain genome stability

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• 作者：Sean G. Rudd ; ¹ ; ^{sean.rudd@scilifelab.se" class="auth_mail" title="E-mail the corresponding author} ; Nicholas C.K. Valerie¹ ; Thomas Helleday ; ^{thomas.helleday@scilifelab.se" class="auth_mail" title="E-mail the corresponding author}
• 关键词：BER ; base excision repair ; CDA ; cytidine deaminase ; MMR ; mis-match repair ; MTH ; MutT homologue ; MUTYH ; MutY homologue ; Nudix ; nucleoside diphosphate linked to some other moiety ; X ; NUDT ; Nudix-type ; OGG1 ; 8-oxoguanine glycosylase ; ROS ; reactive oxygen species ; 8-oxo(d)GTP ; 7 ; 8-dihydro-8-oxo-(2´ ; -deoxy)guanosine-5´ ; -triphosphate ; 2-OH(d)ATP ; 2-hydroxy(2&prime ; -deoxy)adenosine-5´ ; -triphosphate ; 6-thio(d)GTP ; 6-thio-(2&prime ; -deoxy)guanosine-5&prime ; -triphosphate ; PCNA ; proliferating
• 刊名：DNA Repair
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：44
• 期：Complete
• 页码：193-204
• 全文大小：1808 K

文摘

Artificially modified nucleotides, in the form of nucleoside analogues, are widely used in the treatment of cancers and various other diseases, and have become important tools in the laboratory to characterise DNA repair pathways. In contrast, the role of endogenously occurring nucleotide modifications in genome stability is little understood. This is despite the demonstration over three decades ago that the cellular DNA precursor pool is orders of magnitude more susceptible to modification than the DNA molecule itself. More recently, underscoring the importance of this topic, oxidation of the cellular nucleotide pool achieved through targeting the sanitation enzyme MTH1, appears to be a promising anti-cancer strategy. This article reviews our current understanding of modified DNA precursors in genome stability, with a particular focus upon oxidised nucleotides, and outlines some important outstanding questions.