Efficient repair of A/C mismatches in mouse cells deficient in long-patch mismatch repair

A previously unrecognized mismatch repair activity is described. Extracts o f immortalized MSH2-deficient mouse fibroblasts did not correct most single base mispairs. The same extracts carried out efficient repair of A/C misma tches. A/G mispairs were less efficiently corrected and there was no signif icant repair of A/A. MLH1-defective mouse extracts also repaired an A/C mis pair. A/C correction by Msh2(-/-) mouse cell extracts was not affected by a ntibodies against the PMS2 protein, which inhibited long-patch mismatch rep air. A/C repair activity is thus independent of MutS alpha, MutS beta and M utL alpha. A/C mismatches were corrected 5-fold more efficiently by extract s of Msh2 knockout mouse cells than by comparable extracts prepared from hM SH2- or hMLH1-deficient human cells, MSH2-independent A/C correction by mou se cell extracts did not require a nick in the circular duplex DNA substrat e. Repair involved replacement of the A and was associated with the resynth esis of a limited stretch of less than or equal to 25 bases of DNA.