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Query: EC:3.2.1.143 (poly(ADP-ribose) glycohydrolase)
 208 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Poly(ADP-ribose) built from NAD+ on histones and other nuclear proteins by poly(ADP-ribose) polymerase is involved in repair, replication, gene expression, recombination, and chromatin remodeling in embryogenesis. Such nuclear processes are believed to be facilitated by opening up of condensed chromatin structures and by removal of histones from DNA at damaged sites as well as at origins of replication and transcription initiation sites. In addition, poly(ADP-ribosyl)ation might be involved in the up or down regulation of the activity of key nuclear enzymes. Poly(ADP-ribose) is rapidly synthesized at sites containing DNA strand breaks and is then rapidly degraded (half-life 0.5-5 min) by poly(ADP-ribose)glycohydrolase. High-resolution polyacrylamide gel electrophoresis is used in this study to analyze the rate of consumption of [32P]NAD+, the rate of formation of poly(ADP-ribose) molecules, and the rate of appearance of ADP-ribose, AMP, and phosphoribosyl-AMP, the catabolites of poly(ADP-ribose) in isolated nuclei from mouse cells in culture. Our method permits direct loading of aliquots of nuclei at time intervals on the polyacrylamide gel. The action of poly(ADP-ribose) glycohydrolase that degrades the polymer starts at less than 2 min from polymer formation. A poly(ADP-ribose) phosphodiesterase present in mammalian cell nuclei begins degrading poly(ADP-ribose) or unincorporated NAD+ and free ADP-ribose at 10 min. Mammalian phosphodiesterase is identified as an enzyme more important than previously thought which might degrade poly(ADP-ribosyl)ated proteins but also recycle the ADP-ribose produced from di- to poly(ADP-ribosyl)ated proteins by glycohydrolase into utilizable AMP units.
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PMID:Poly(ADP-ribose) synthesis and degradation in mammalian nuclei. 132 75

Poly(ADP-ribose) polymerase and poly(ADP-ribose) glycohydrolase have been detected in chromatin extracts from the dinoflagellate Crypthecodinium cohnii. Poly(ADP-ribose) glycohydrolase was detected by the liberation of ADP-ribose from poly(ADP-ribose). Poly(ADP-ribose) polymerase was proved by (a) demonstration of phosphoribosyl-AMP in the phosphodiesterase digest of the reaction product, (b) demonstration of ADP-ribose oligomers by fractionation of the reaction product on DEAE-Sephadex. The (ADP-ribose)-protein transfer is dependent on DNA; it is inhibited by nicotinamide, thymidine, theophylline and benzamide. The protein-(ADP-ribose bond is susceptible to 0.1 M NaOH (70%) and 0.4 M NH2OH (33%). Dinoflagellates, nucleated protists, are unique in that their chromatin lacks histones and shows a conformation like bacterial chromatin [Loeblich, A. R., III (1976) J. Protozool. 23, 13--28]; poly(ADP-ribose) polymerase, however, has been found only in eucaryotes. Thus our results suggest that histones were not relevant to the establishment of poly(ADP-ribose) during evolution.
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PMID:Presence of poly (ADP-ribose) polymerase and poly (ADP-ribose) glycohydrolase in the dinoflagellate Crypthecodinium cohnii. 632 Nov 75

The nuclear metabolism of poly(ADP-ribose) is mainly regulated by poly(ADP-ribose) polymerase-1 (PARP-1) and by poly(ADP-ribose) glycohydrolase (PARG). A PARP-like enzyme, V-PARP, and a PARG isoform are present in the extra-nuclear compartment of mammalian cells, even if poly(ADP-ribose) has never been detected therein. In this work, we demonstrate the ability of post-nuclear extracts from HeLa and HL60 cells to degrade synthetic 32P-polymers of ADP-ribose to ADP-ribose and, further, to AMP. This reaction implies the combined action of PARG and of an ADP-ribose-degrading activity, possibly corresponding to a phosphodiesterase and/or to an ADP-ribose pyrophosphatase. The inhibition of PARG or ADP-ribose-degrading enzymes allowed the demonstration that in vitro synthesized 32P-poly(ADP-ribose) is first digested to ADP-ribose monomers by a typical PARG reaction, and that ADP-ribose is further rapidly converted into AMP by an Mg(2+)-dependent activity. Collectively, our results demonstrate the ability of the human cell post-nuclear fraction to convert synthetic poly(ADP-ribose) into utilizable AMP units by the concerted action of PARG and ADP-ribose-degrading activities.
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PMID:Poly(ADP-ribose) degradation by post-nuclear extracts from human cells. 1262

Upon massive DNA damage, hyperactivation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP)-1 causes severe depletion of intracellular NAD and ATP pools as well as mitochondrial dysfunction. Thus far, the molecular mechanisms contributing to PARP-1-dependent impairment of mitochondrial functioning have not been identified. We found that degradation of the PARP-1 product poly(ADP-ribose) through the concerted actions of poly(ADP-ribose) glycohydrolase and NUDIX (nucleoside diphosphate-X) hydrolases leads to accumulation of AMP. The latter, in turn, inhibits the ADP/ATP translocator, prompting mitochondrial energy failure. For the first time, our findings identify NUDIX hydrolases as key enzymes involved in energy derangement during PARP-1 hyperactivity. Also, these data disclose unanticipated AMP-dependent impairment of mitochondrial exchange of adenine nucleotides, which can be of relevance to organelle functioning and disease pathogenesis.
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PMID:Poly(ADP-ribose) catabolism triggers AMP-dependent mitochondrial energy failure. 1941 Dec 52