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  • The EMBO Journal (2000) 19, 1711 - 1718
  • doi:10.1093/emboj/19.7.1711

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

S. Oda1,4, O. Humbert2,4, S. Fiumicino3, M. Bignami3 and P. Karran1

  1. Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK
  2. Present address: IPBS du CNRS, 205 Route de Narbonne, 31077 Toulouse Cedex, France
  3. Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome, Italy
  4. S.Oda and O.Humbert contributed equally to this work

Correspondence to:

P. Karran, E-mail: P.Karran@icrf.icnet.uk

Received 3 November 1999; Accepted 4 February 2000; Revised 2 February 2000

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 MutSalpha, MutSbeta and MutLalpha. 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 less than or equal to25 bases of DNA.

  • Keywords:

    • A/C mispairs,
    • mismatch repair,
    • Msh2 knockout mice