title: On the biological role of the nuclear polymerizing NAD+: protein(ADP-ribosyl) transferase (ADPRT): ADPRT from Dictyostelium discoideum and inactivation of the ADPRT gene in the mouse.
abstract: Two approaches have been used to elucidate the role of the nuclear polymerizing NAD+:protein(ADP-ribosyl)-transferase (ADPRT): i) comparison of the primary structure of Dictyostelium discoideum ADPRT derived from a 2 kb, partial cDNA sequence with the mammalian, fish, amphibian and insect counterparts revealed an overall homology of 25%. Whereas the automodification domain was not conserved at all, the NAD+ binding domain (aa 859-908) showed more than 70% identical amino acids in all species. Together with the similar enzymatic properties of the ADPRTs the genetic conservation underlined the notion that ADPRT plays a major role in various cellular processes; and ii) inactivation of the ADPRT gene in murine embryonic stem cells by homologous recombination led to mouse strains with a complete lack of nuclear poly(ADP-ribosyl)ation. These ADPRT mutant mice were viable and fertile indicating that ADPRT is dispensable in mouse development. Moreover, repair of UV and MNNG induced DNA damage was not affected in ADPRT/3T3 like fibroblasts, as measured by reactivation of in vitro damaged reporter plasmids and unscheduled DNA synthesis. However, about 30% of the ADPRT mutant mice developed pathological skin aberrations on a mixed 129/Sv x C57B1/6 genetic background. These mice will be extremely useful to define the precise biological role of poly(ADP-ribosyl)ation.
authors.affiliation: Institute of Biochemistry, University of Innsbruck, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Auer
authors.forename: K
authors.initials: K
authors.lastname: Flick
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Wang
authors.forename: D
authors.initials: D
authors.lastname: Haidacher
authors.forename: S
authors.initials: S
authors.lastname: Jäger
authors.forename: H
authors.initials: H
authors.lastname: Berghammer
authors.forename: B
authors.initials: B
authors.lastname: Kofler
authors.forename: M
authors.initials: M
authors.lastname: Schweiger
authors.forename: E F
authors.initials: EF
authors.lastname: Wagner
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics / Q000502:physiology*; D000375:Aging / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology*; D003001:Cloning, Molecular; D004023:Dictyostelium / Q000201:enzymology*; D005298:Fertility / Q000235:genetics; D005800:Genes, Fungal; D006965:Hyperplasia / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011065:Poly(ADP-ribose) Polymerases; D011995:Recombination, Genetic; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000473:pathology; D013234:Stem Cells / Q000502:physiology
chemical_list: D036002:ADP Ribose Transferases; D011065:Poly(ADP-ribose) Polymerases