Mismatch repair proteins MutS and MutL inhibit RecA-catalyzed strand transfer between diverged DNAs.

Bacterial mutS and mutL mutations confer large increases in recombination between sequences that are divergent by several percent at the nucleotide level, an effect attributed to a role for products of these genes in control of recombination fidelity. Since MutS and MutL are proteins involved in the earliest steps of mismatch repair, including mismatch recognition by MutS, we have tested the possibility that they may affect strand exchange in response to occurrence of mispairs within the recombination heteroduplex. We show that MutS abolishes RecA-catalyzed strand transfer between fd and M13 bacteriophage DNAs, which vary by 3% at the nucleotide level, but is without effect on M13-M13 or fd-fd exchange. Although MutL alone has no effect on M13-fd heteroduplex formation, the protein dramatically enhances the inhibition of strand transfer mediated by MutS. Analysis of strand-transfer intermediates that accumulate in the presence of MutS and MutL indicates that the proteins block branch migration, presumably in response to occurrence of mispairs within newly formed heteroduplex.