Model for postreplicative mismatch correction of DNA. GATC sequences in DNA are normally methylated (Me) at the 6 position of adenine. During semiconservative DNA synthesis, a G-T mismatch arises in one of the sister DNA duplexes. The enzymatic mechanism for repairing this lesion depends on discrimination between the newly synthesized (red) and parental (black) strands. This is achieved by recognition of the transient lack of methylation of the newly synthesized strand before postreplicative DNA methylation takes place. The nonmethylated daughter strand containing the incorrect base is enzymatically attacked by mismatch correction enzymes, and the misincorporated base is excised. Repair synthesis and daughter-strand methylation at GATC sequences restore the sister DNA duplexes to their native state.