A human DNA editing enzyme homologous to the Escherichia coli DnaQ/MutD protein

Mammalian DNA polymerases alpha and beta lack 3' exonuclease activity and a re unable to edit errors after DNA synthesis. However, editing exonucleases can be functions of separate polypeptides. We isolated a widely distribute d DNA-specific 3' exonuclease from rabbit liver nuclei, sequenced tryptic p eptides by mass spectrometry, and identified the corresponding human open r eading frame, The protein expressed from the cloned human sequence exhibits 3' exonuclease activity. The human clone shares sequence homology with the editing function of the Escherichia coli DNA polymerase III holoenzyme, i. e., the DnaQ/MutD protein, and weakly with the editing 3' exonuclease domai n of eukaryotic DNA polymerase epsilon. The gene maps to human chromosome 3 p21.2-21.3. In a reconstituted human DNA repair system containing DNA polym erase beta and DNA ligase III-XRCC1, accurate rejoining of a 3' mismatched base residue at single-strand break is dependent on addition of the exonucl ease.