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.
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.
Auer
B
B
Institute of Biochemistry, University of Innsbruck, Austria.
Flick
K
K
Wang
Z Q
ZQ
Haidacher
D
D
Jäger
S
S
Berghammer
H
H
Kofler
B
B
Schweiger
M
M
Wagner
E F
EF
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
D036002:ADP Ribose Transferases; D011065:Poly(ADP-ribose) Polymerases