A human DNA editing enzyme homologous to the Escherichia coli DnaQ/MutD protein.
Mammalian DNA polymerases alpha and beta lack 3' exonuclease activity and are unable to edit errors after DNA synthesis. However, editing exonucleases can be functions of separate polypeptides. We isolated a widely distributed DNA-specific 3' exonuclease from rabbit liver nuclei, sequenced tryptic peptides by mass spectrometry, and identified the corresponding human open reading 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 domain of eukaryotic DNA polymerase epsilon. The gene maps to human chromosome 3p21.2-21.3. In a reconstituted human DNA repair system containing DNA polymerase beta and DNA ligase III-XRCC1, accurate rejoining of a 3' mismatched base residue at a single-strand break is dependent on addition of the exonuclease.
Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK.
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Höss
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Robins
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Naven
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Pappin
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Sgouros
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Lindahl
D000595:Amino Acid Sequence; D000818:Animals; D020137:Base Pair Mismatch / Q000235:genetics; D002384:Catalysis; D002467:Cell Nucleus / Q000201:enzymology; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D003001:Cloning, Molecular; D011088:DNA Ligases / Q000378:metabolism; D004257:DNA Polymerase II / Q000737:chemistry / Q000235:genetics; D004258:DNA Polymerase III; D019951:DNA Polymerase beta / Q000378:metabolism; D004260:DNA Repair / Q000235:genetics; D004277:DNA, Single-Stranded / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics*; D029968:Escherichia coli Proteins; D043211:Exodeoxyribonuclease V; D005090:Exodeoxyribonucleases / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D008970:Molecular Weight; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D004277:DNA, Single-Stranded; D029968:Escherichia coli Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D004257:DNA Polymerase II; D004258:DNA Polymerase III; D019951:DNA Polymerase beta; C468316:dnaQ protein, E coli; D005090:Exodeoxyribonucleases; C020133:exodeoxyribonuclease III; D043211:Exodeoxyribonuclease V; D011088:DNA Ligases