The repair o
f T:G mismatches in DNA is key
for maintaining bacterial restriction/modi
fication systems and gene silencing in higher eukaryotes. T:G mismatch repair can be initiated by a speci
fic mismatch glycosylase (MIG) that is homologous to the helix-hairpin-helix (HhH) DNA repair enzymes. Here, we present a 2.0 Å resolution crystal structure and complementary mutagenesis results
for this thermophilic HhH MIG enzyme. The results suggest that MIG distorts the target thymine nucleotide by twisting the thymine base
![](/images/glyphs/BQ1.GIF)
90° away
from its normal
anti position within DNA. We propose that
functionally signi
ficant di
fferences exist in DNA repair enzyme extrahelical nucleotide binding and catalysis that are characteristic o
f whether the target base is damaged or is a normal base within a mispair. These results explain why pure HhH DNA glycosylases and combined glycosylase/AP lyases cannot be interconverted by simply altering their
functional group chemistry, and how broad-speci
ficity DNA glycosylase enzymes may weaken the glycosylic linkage to allow a variety o
f damaged DNA bases to be excised.