A.T----C.G transversions and their prevention by the Escherichia coli mutT and mutHLS pathways

Escherichia coli mutT strains are strong mutators yielding only A.T----C.G transversion mutations. These are thought to result from uncorrected (or unprevented) A.G mispairings during DNA replication. We have investigated the interaction of mutT-induced replication errors with the mutHLS-encoded postreplicative mismatch repair system. By measuring mutation frequencies in both forward and reversion systems, we have demonstrated that mutTmutL and mutTmutS double mutators produce no more mutants than expected from simple additivity of the frequencies in the single mutators. We conclude that mutT-induced A.G replication errors are not recognized by the MutHLS system. On the other hand, direct measurements of mismatch repair by transfection of bacteriophage M13mp2 heteroduplex DNA as well as mutational data from strains other than muT, indicate that the MutHLS system can repair at least certain A.G mispairs. We suggest that A.G mispairs may exist in several different conformations, some of which are recognized by the MutHLS system. However, the A.G mispairs normally prevented by the mutT function are refractory to mismatch repair, indicating that they may represent a structurally distinct class.