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

MSH2 and MSH6 Are Required for Removal of Adenine Misincorporated Opposite 8-oxo-guanine in S. Cerevisiae

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MSH2 and MSH6 Are Required for Removal of Adenine Misincorporated Opposite 8-oxo-guanine in S. Cerevisiae

T T Ni et al. Mol Cell. .

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.

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