Mechanism of DNA polymerase II-mediated frameshift mutagenesis

Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8566-71. doi: 10.1073/pnas.141113398. Epub 2001 Jul 10.


Escherichia coli possesses three SOS-inducible DNA polymerases (Pol II, IV, and V) that were recently found to participate in translesion synthesis and mutagenesis. Involvement of these polymerases appears to depend on the nature of the lesion and its local sequence context, as illustrated by the bypass of a single N-2-acetylaminofluorene adduct within the NarI mutation hot spot. Indeed, error-free bypass requires Pol V (umuDC), whereas mutagenic (-2 frameshift) bypass depends on Pol II (polB). In this paper, we show that purified DNA Pol II is able in vitro to generate the -2 frameshift bypass product observed in vivo at the NarI sites. Although the Delta polB strain is completely defective in this mutation pathway, introduction of the polB gene on a low copy number plasmid restores the -2 frameshift pathway. In fact, modification of the relative copy number of polB versus umuDC genes results in a corresponding modification in the use of the frameshift versus error-free translesion pathways, suggesting a direct competition between Pol II and V for the bypass of the same lesion. Whether such a polymerase competition model for translesion synthesis will prove to be generally applicable remains to be confirmed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Acetylaminofluorene / pharmacology
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Binding Sites
  • DNA Adducts*
  • DNA Polymerase II / genetics
  • DNA Polymerase II / metabolism*
  • DNA Replication*
  • Deoxyribonucleases, Type II Site-Specific / metabolism
  • Escherichia coli / enzymology*
  • Escherichia coli / genetics
  • Escherichia coli Proteins*
  • Frameshift Mutation*
  • Gene Expression
  • Plasmids
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism


  • Bacterial Proteins
  • DNA Adducts
  • Escherichia coli Proteins
  • Recombinant Fusion Proteins
  • polB protein, E coli
  • 2-Acetylaminofluorene
  • DNA Polymerase II
  • Deoxyribonucleases, Type II Site-Specific
  • GGCGCC-specific type II deoxyribonucleases