Overexpression of DNA polymerase beta results in an increased rate of frameshift mutations during base excision repair

Mutagenesis. 2007 May;22(3):183-8. doi: 10.1093/mutage/gel070. Epub 2007 Jan 31.


DNA polymerase beta (Pol beta) is important for the base excision repair (BER) pathway. Overexpression of Pol beta is frequently found in cancer cells and is thought to be associated with tumorigenesis. In this study, we examined BER fidelity in extracts derived from a human lymphoblastoid cell line that over expresses Pol beta compared to normal control cells. Using an in vitro mutagenesis assay, we found an increased rate of frameshift mutations arising during DNA repair in whole-cell extracts derived from the Pol beta-overexpressing cells. We demonstrate that the addition of excess Pol beta to a control cell extract enhances the mutagenic potential of the extract. Furthermore, using cell extracts and purified Pol beta, we demonstrate that the mechanism of frameshift formation involves slippage of Pol beta during the one-nucleotide gap-filling step of BER and that this slippage is fixed by strand-displacement synthesis stimulated by an excess of Pol beta.

Publication types

  • Comparative Study

MeSH terms

  • Base Sequence
  • Blotting, Western
  • Cell Line, Tumor
  • DNA Polymerase beta / metabolism
  • DNA Polymerase beta / pharmacology*
  • DNA Repair / physiology*
  • DNA Replication / physiology
  • Escherichia coli
  • Frameshift Mutation / drug effects*
  • Frameshift Mutation / physiology
  • Gene Expression Regulation, Enzymologic / physiology
  • Humans
  • Molecular Sequence Data
  • Oligonucleotides


  • Oligonucleotides
  • DNA Polymerase beta