MSH2 and MSH6 are required for removal of adenine misincorporated opposite 8-oxo-guanine in S. cerevisiae

Mol Cell. 1999 Sep;4(3):439-44. doi: 10.1016/s1097-2765(00)80346-9.

Abstract

Oxidation of G in DNA yields 8-oxo-G (GO), a mutagenic lesion that leads to misincorporation of A opposite GO. In E. coli, GO in GO:C base pairs is removed by MutM, and A in GO:A mispairs is removed by MutY. In S. cerevisiae, mutations in MSH2 or MSH6 caused a synergistic increase in mutation rate in combination with mutations in OGG1, which encodes a MutM homolog, resulting in a 140- to 218-fold increase in the G:C-to-T:A transversion rate. Consistent with this, MSH2-MSH6 complex bound to GO:A mispairs and GO:C base pairs with high affinity and specificity. These data indicate that in S. cerevisiae, MSH2-MSH6-dependent mismatch repair is the major mechanism by which misincorporation of A opposite GO is corrected.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenine / metabolism*
  • Base Pair Mismatch*
  • DNA Damage
  • DNA Repair*
  • DNA-Binding Proteins / metabolism
  • Fungal Proteins / metabolism*
  • Guanine / analogs & derivatives*
  • Guanine / metabolism
  • Models, Genetic
  • MutS Homolog 2 Protein
  • Mutagenesis
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins*

Substances

  • DNA-Binding Proteins
  • Fungal Proteins
  • MSH6 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • 8-hydroxyguanine
  • Guanine
  • MSH2 protein, S cerevisiae
  • MutS Homolog 2 Protein
  • Adenine