Human MutLα: The jack of all trades in MMR is also an endonuclease

Recently, Paul Modrich's group reported the discovery of an intrinsic endonuclease activity for human MutLα. This breakthrough provides a satisfactory answer to the longstanding puzzle of a missing nuclease activity in human mismatch repair and will undoubtedly lead to new investigations of DNA repair and replication. Here, the implications of this exciting new finding are discussed in the context of mismatch repair in Escherichia coli and humans.