Mutagenic conformation of 8-oxo-7,8-dihydro-2'-dGTP in the confines of a DNA polymerase active site

Nat Struct Mol Biol. 2010 Jul;17(7):889-90. doi: 10.1038/nsmb.1852. Epub 2010 Jun 6.

Abstract

The major product of oxidative base damage is 8-oxo-7,8-dihydro-2'-deoxyguanine (8odG). The coding potential of this lesion is modulated by its glycosidic torsion angle that controls whether its Watson-Crick or Hoogsteen edge is used for base pairing. The 2.0-A structure of DNA polymerase (pol) beta bound with 8odGTP opposite template adenine indicates that the modified nucleotide assumes the mutagenic syn conformation and that the nonmutagenic anti conformation would be incompatible with efficient DNA synthesis.

Publication types

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

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine / analogs & derivatives
  • Catalytic Domain
  • Crystallography, X-Ray
  • DNA Polymerase beta / chemistry*
  • DNA Polymerase beta / metabolism
  • Guanine / analogs & derivatives*
  • Guanine / chemistry
  • Guanine / metabolism
  • Humans
  • Models, Molecular
  • Molecular Conformation
  • Protein Conformation

Substances

  • Guanine
  • 8-oxo-7,8-dihydrodeoxyguanine
  • 8-Hydroxy-2'-Deoxyguanosine
  • DNA Polymerase beta

Associated data

  • PDB/3MBY