title: The Drosophila melanogaster Gene cg4930 Encodes a High Affinity Inhibitor for Endonuclease G.
abstract: Endonuclease G (EndoG) is a mitochondrial enzyme believed to be released during apoptosis to participate in the degradation of nuclear DNA. This paper describes a Drosophila protein, EndoGI, which inhibits EndoG specifically. EndoG and EndoGI associate with subpicomolar affinity, forming a 2:1 complex in which dimeric EndoG is bound by two tandemly repeated homologous domains of monomeric EndoGI. Binding appears to involve the active site of EndoG. EndoGI is present in the cell nucleus at micromolar concentrations. Upon induction of apoptosis, levels of the inhibitor appear to be reduced, and it is relocalized to the cytoplasm. EndoGI, encoded by the predicted open reading frame cg4930, is expressed throughout Drosophila development. Flies homozygous for a hypomorphic EndoGI mutation have a strongly reduced viability, which is modulated by genetic background and diet. We propose that EndoGI protects the cell against low levels of EndoG outside mitochondria.
authors.affiliation: Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Strasse 3, 06120 Halle, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Temme
authors.forename: Rebekka
authors.initials: R
authors.lastname: Weissbach
authors.forename: Hauke
authors.initials: H
authors.lastname: Lilie
authors.forename: Clive
authors.initials: C
authors.lastname: Wilson
authors.forename: Anton
authors.initials: A
authors.lastname: Meinhart
authors.forename: Sylke
authors.initials: S
authors.lastname: Meyer
authors.forename: Ralph
authors.initials: R
authors.lastname: Golbik
authors.forename: Angelika
authors.initials: A
authors.lastname: Schierhorn
authors.forename: Elmar
authors.initials: E
authors.lastname: Wahle
mesh_terms: D000818:Animals; D002460:Cell Line; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D004706:Endodeoxyribonucleases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; C558783:endonuclease G inhibitor, Drosophila; D004706:Endodeoxyribonucleases; C052391:endonuclease G