In the striatal tissue of HD mice carrying expanded CAG repeats, abasic sites located at the 5' ends of the CAG repeats in a hairpin conformation were repaired less efficiently then abasic sites in B-DNA. Purified MSH2-MSH3 complex can bind to CAG repeats in a hairpin structure, but the ATP hydrolysis activity of MSH2-MSH3 was reduced upon binding to a hairpin structure that contained A-A mis-paired bases in the stem. The effects of other types of mismatches within the triplet repeat have not yet been tested. As mentioned above, guanines in Z-DNA are more sensitive to alkylating modification, and once formed, the lesions in Z-DNA, were resistant to excision by their repair enzymes, DNA glycosylase and 06-methylguanine-DNA methyltransferase, respectively. The persisting damage in non-B DNA conformations could result in hotpots for genetic instability.