RRC ID 30456
Author Hanai S, Kanai M, Ohashi S, Okamoto K, Yamada M, Takahashi H, Miwa M.
Title Loss of poly(ADP-ribose) glycohydrolase causes progressive neurodegeneration in Drosophila melanogaster.
Journal Proc Natl Acad Sci U S A
Abstract Poly(ADP-ribosyl)ation has been suggested to be involved in regulation of DNA repair, transcription, centrosome duplication, and chromosome stability. However, the regulation of degradation of poly(ADP-ribose) and its significance are not well understood. Here we report a loss-of-function mutant Drosophila with regard to poly(ADP-ribose) glycohydrolase, a major hydrolyzing enzyme of poly(ADP-ribose). The mutant lacks the conserved catalytic domain of poly(ADP-ribose) glycohydrolase, and exhibits lethality in the larval stages at the normal development temperature of 25 degrees C. However, one-fourth of the mutants progress to the adult stage at 29 degrees C but showed progressive neurodegeneration with reduced locomotor activity and a short lifespan. In association with this, extensive accumulation of poly(ADP-ribose) could be detected in the central nervous system. These results suggest that poly(ADP-ribose) metabolism is required for maintenance of the normal function of neuronal cells. The phenotypes observed in the parg mutant might be useful to understand neurodegenerative conditions such as the Alzheimer's and Parkinson's diseases that are caused by abnormal accumulation of substances in nervous tissue.
Volume 101(1)
Pages 82-6
Published 2004-1-6
DOI 10.1073/pnas.2237114100
PII 2237114100
PMID 14676324
PMC PMC314142
MeSH Animals Base Sequence Brain / ultrastructure DNA / genetics Drosophila melanogaster / enzymology* Drosophila melanogaster / genetics Drosophila melanogaster / growth & development Female Genes, Insect Glycoside Hydrolases / deficiency* Glycoside Hydrolases / genetics Glycoside Hydrolases / physiology Humans Male Microscopy, Electron Mutation Nerve Degeneration / enzymology* Nerve Degeneration / genetics Nerve Degeneration / pathology Phenotype Temperature
IF 9.412
Times Cited 146
Drosophila DGRC#109112