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

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Abstract
A previously unrecognized mismatch repair activity is described. Extracts of immortalized MSH2‐deficient mouse fibroblasts did not correct most single base mispairs. The same extracts carried out efficient repair of A/C mismatches. A/G mispairs were less efficiently corrected and there was no significant repair of A/A. MLH1‐defective mouse extracts also repaired an A/C mispair. A/C correction by Msh2−/− mouse cell extracts was not affected by antibodies against the PMS2 protein, which inhibited long‐patch mismatch repair. A/C repair activity is thus independent of MutSα, MutSβ and MutLα. A/C mismatches were corrected 5‐fold more efficiently by extracts of Msh2 knockout mouse cells than by comparable extracts prepared from hMSH2‐ or hMLH1‐deficient human cells. MSH2‐independent A/C correction by mouse cell extracts did not require a nick in the circular duplex DNA substrate. Repair involved replacement of the A and was associated with the resynthesis of a limited stretch of ≤25 bases of DNA.