Pathways controlling dNTP pools to maintain genome stability

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 modificati...

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Bibliographic Details
Published in:DNA repair 2016-08, Vol.44, p.193-204
Main Authors: Rudd, Sean G., Valerie, Nicholas C.K., Helleday, Thomas
Format: Article
Language:English
Subjects:
DNA - chemistry
DNA - genetics
DNA - metabolism
DNA Damage
DNA polymerase
DNA Repair
DNA Repair Enzymes - genetics
DNA Repair Enzymes - metabolism
dNTP pool sanitation
Genome stability
Genome, Human
Genomic Instability
Humans
Medicin och hälsovetenskap
MTH1
Nucleic Acid Precursors - chemistry
Nucleic Acid Precursors - genetics
Nucleic Acid Precursors - metabolism
Nucleotides - biosynthesis
Nucleotides - chemistry
Nudix Hydrolases
Oxidation-Reduction
Oxidative Stress
Oxidised nucleotides
Phosphoric Monoester Hydrolases - genetics
Phosphoric Monoester Hydrolases - metabolism
Pyrophosphatases - genetics
Pyrophosphatases - metabolism
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Summary: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.
ISSN:1568-7864
1568-7856
1568-7856
DOI:10.1016/j.dnarep.2016.05.032