title: The Saccharomyces cerevisiae LYS7 gene is involved in oxidative stress protection.
abstract: Saccharomyces cerevisiae Lys7p was proposed to be the enzyme catalyzing the dehydratation of homocitrate to cis-homoaconitate, the second step of the lysine biosynthetic pathway. In this communication we provide evidence that Lys7p is involved in oxidative stress protection. Cells deleted for the LYS7 gene displayed, in addition to lysine auxotrophy, methionine auxotrophy, sensitivity to superoxide generating drugs and light irradiation, and diminution of calcineurin activity. The SOD1 gene encoding the Cu/Zn-superoxide dismutase was expressed in strains lacking Lys7p, and although Sodlp was produced in normal amounts no detectable enzyme activity was found. In contrast, the mitochondrial Mn-superoxide dismutase activity did not seem to be impaired. lys7 cells exhibited a normal uptake of Cu from growth medium. The Cu/Zn-superoxide dismutase activity was restored by addition of Cu (but not by addition of other metallic cations) to the growth medium or to cellular extracts, suggesting a lack of Cu2+ at the active site. These results render it necessary to reconsider the role of the Lys7p. Its involvement in Cu metabolism and oxidative-stress protection, and the possibility of a human equivalent in amyotrophic lateral sclerosis are discussed.
authors.affiliation: Institut de Biochimie et Génétique Cellulaires, Centre National de la Recherche Scientifique, Bordeaux, France.
authors.forename: F
authors.initials: F
authors.lastname: Gamonet
authors.forename: G J
authors.initials: GJ
authors.lastname: Lauquin
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics; D003300:Copper / Q000378:metabolism / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D005656:Fungal Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D008239:Lysine / Q000378:metabolism; D008715:Methionine / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D018384:Oxidative Stress / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D013481:Superoxides / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D007527:Isoenzymes; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins; D013481:Superoxides; D003300:Copper; D008715:Methionine; C095735:LYS7 protein, S cerevisiae; D013482:Superoxide Dismutase; D008239:Lysine