title: EXOG, a novel paralog of Endonuclease G in higher eukaryotes.
abstract: Evolutionary conserved mitochondrial nucleases are involved in programmed cell death and normal cell proliferation in lower and higher eukaryotes. The endo/exonuclease Nuc1p, also termed 'yeast Endonuclease G (EndoG)', is a member of this class of enzymes that differs from mammalian homologs by the presence of a 5'-3' exonuclease activity in addition to its broad spectrum endonuclease activity. However, this exonuclease activity is thought to be essential for a function of the yeast enzyme in DNA recombination and repair. Here we show that higher eukaryotes in addition to EndoG contain its paralog 'EXOG', a novel EndoG-like mitochondrial endo/exonuclease. We find that during metazoan evolution duplication of an ancestral nuclease gene obviously generated the paralogous EndoG- and EXOG-protein subfamilies in higher eukaryotes, thereby maintaining the full endo/exonuclease activity found in mitochondria of lower eukaryotes. We demonstrate that human EXOG is a dimeric mitochondrial enzyme that displays 5'-3' exonuclease activity and further differs from EndoG in substrate specificity. We hypothesize that in higher eukaryotes the complementary enzymatic activities of EndoG and EXOG probably together account for both, the lethal and vital functions of conserved mitochondrial endo/exonucleases.
authors.affiliation: Laboratory of Bioinformatics and Protein Engineering, International Institute of Molecular and Cell Biology, Trojdena 4, 02-109 Warsaw, Poland.
authors.forename: Iwona A
authors.initials: IA
authors.lastname: Cymerman
authors.forename: Inn
authors.initials: I
authors.lastname: Chung
authors.forename: Benedikt M
authors.initials: BM
authors.lastname: Beckmann
authors.forename: Janusz M
authors.initials: JM
authors.lastname: Bujnicki
authors.forename: Gregor
authors.initials: G
authors.lastname: Meiss
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D002460:Cell Line; D019281:Dimerization; D004706:Endodeoxyribonucleases / Q000737:chemistry; D004720:Endonucleases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005092:Exonucleases / Q000378:metabolism; D006639:Histidine / Q000235:genetics; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051336:Mitochondrial Membranes / Q000201:enzymology*; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D016415:Sequence Alignment; D013379:Substrate Specificity
chemical_list: D024101:Mitochondrial Proteins; D006639:Histidine; C523510:EXOG protein, human; D004706:Endodeoxyribonucleases; D004720:Endonucleases; D005092:Exonucleases; C052391:endonuclease G