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

• Published in: The EMBO journal 2000-04, Vol.19 (7), p.1711-1718
• Main Authors: Oda, S., Humbert, O., Fiumicino, S., Bignami, M., Karran, P.
• Format: Article
• Language: English
• Subjects: A/C mispairs; Adaptor Proteins, Signal Transducing; Animals; Base Pair Mismatch; Base Sequence; Carrier Proteins; Cell Line; Deoxyribonucleic acid; DNA; DNA Primers - genetics; DNA Repair; DNA-Binding Proteins; HeLa Cells; Humans; Mice; Mice, Knockout; mismatch repair; MSH2 gene; Msh2 knockout mice; MutL Protein Homolog 1; MutLa protein; MutS Homolog 2 Protein; MutSa protein; MutSb protein; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Nuclear Proteins; PMS2 protein; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1093/emboj/19.7.1711

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.