Altered DNA damage response in Caenorhabditis elegans with impaired poly(ADP-ribose) glycohydrolases genes expression

摘要: Abstract Poly(ADP-ribosyl)ation is one of the first cellular responses induced by DNA damage. Poly(ADP-ribose) rapidly synthesized nick-sensor poly(ADP-ribose) polymerases, which facilitate repair enzymes to process ADP-ribose polymers are catabolized into free units glycohydrolase (PARG). The metabolism a well-defined biochemical for physiological role in animals just beginning emerge. Two Caenorhabditis elegans PARGs, PME-3 and PME-4, have been cloned our group. pme-3 gene encodes an enzyme 89 kDa having less than 18% overall identity with human PARG but 42% signature motif. pme-4 codes 55 kDa approximately 22% 40% alternatively spliced forms were identified SL1 splice leader on both mRNA found be expressed throughout worm's life cycle. Similarly, was shown all developmental stages worm. Recombinant that bacteria displayed activity may partly account measured total worm extract. Reporter analysis using GFP fusion construct showed mainly nerve cells. nuclear while PME-4 localized cytoplasm. Worms expression knocked-down RNAi significant sensitivity toward ionizing radiations. Taken together, these data provide evidence PARGs damage response survival. It also shows evolutionarily conserved they part ancient