The mismatch repair process corrects errors in newly synthesized DNA. In this issue, Modrich and colleagues (Kadyrov et al., 2006) show that a component of the human mismatch repair machinery, MutLα, has endonuclease activity. MutLα introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXOI to degrade the strand containing the mismatch.