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Pathways controlling dNTP pools to maintain genome stability

Sean G Rudd1, Nicholas C K Valerie1, Thomas Helleday1

  • 1Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

DNA Repair
|June 18, 2016
PubMed

Insights

Endogenously modified nucleotides, particularly oxidized forms, significantly impact genome stability. Targeting cellular nucleotide pool oxidation is a promising anti-cancer strategy.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genetics

Background:

  • Artificially modified nucleotides (nucleoside analogues) are crucial in cancer therapy and laboratory research.
  • The role of naturally occurring nucleotide modifications in genome stability remains poorly understood.
  • The cellular DNA precursor pool is highly susceptible to modification.

Purpose of the Study:

  • To review the current understanding of modified DNA precursors in maintaining genome stability.
  • To highlight the significance of oxidized nucleotides.
  • To identify outstanding questions in the field.

Main Methods:

  • Literature review focusing on endogenous nucleotide modifications and genome stability.
  • Analysis of research on oxidized nucleotides and their impact.
  • Discussion of targeting cellular nucleotide pool oxidation.

Main Results:

  • Endogenously modified nucleotides, especially oxidized forms, play a critical role in genome stability.
  • Oxidation of the cellular nucleotide pool is a viable anti-cancer strategy.
  • Significant knowledge gaps exist regarding endogenous nucleotide modification impacts.

Conclusions:

  • Endogenous nucleotide modifications are vital for genome stability.
  • Targeting nucleotide pool oxidation presents a promising therapeutic avenue for cancer treatment.
  • Further research is needed to fully elucidate the mechanisms and implications of endogenous nucleotide modifications.
Keywords:
DNA polymeraseDNA repairGenome stabilityMTH1Oxidised nucleotidesdNTP pool sanitation

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