Lesion processing: high-fidelity versus lesion-bypass DNA polymerases

Trends Biochem Sci. 2008 May;33(5):209-19. doi: 10.1016/j.tibs.2008.02.004. Epub 2008 Apr 11.


When a high-fidelity DNA polymerase encounters certain DNA-damage sites, its progress can be stalled and one or more lesion-bypass polymerases are recruited to transit the lesion. Here, we consider two representative types of lesions: (i) 7,8-dihydro-8-oxoguanine (8-oxoG), a small, highly prevalent lesion caused by oxidative damage; and (ii) bulky lesions derived from the environmental pre-carcinogen benzo[a]pyrene, in the high-fidelity DNA polymerase Bacillus fragment (BF) from Bacillus stearothermophilus and in the lesion-bypass DNA polymerase IV (Dpo4) from Sulfolobus solfataricus. The tight fit of the BF polymerase around the nascent base pair contrasts with the more spacious, solvent-exposed active site of Dpo4, and these differences in architecture result in distinctions in their respective functions: one-step versus stepwise polymerase translocation, mutagenic versus accurate bypass of 8-oxoG, and polymerase stalling versus mutagenic bypass at bulky benzo[a]pyrene-derived lesions.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Base Pair Mismatch
  • Benzo(a)pyrene / pharmacology
  • DNA / drug effects
  • DNA Damage
  • DNA Polymerase beta / physiology
  • DNA Repair / physiology*
  • DNA-Directed DNA Polymerase / physiology*
  • Guanine / analogs & derivatives
  • Guanine / metabolism
  • Models, Molecular
  • Protein Transport
  • Sulfolobus solfataricus / enzymology


  • 7,8-dihydro-8-oxoguanine
  • Benzo(a)pyrene
  • Guanine
  • DNA
  • DNA Polymerase beta
  • DNA-Directed DNA Polymerase