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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) polymerase and poly(ADP-ribose) glycohydrolase activities were both investigated in chicken erythroblasts transformed by Avian Erythroblastosis Virus. Respectively 21% and 58% of these activities were found to be present in the post-mitochondrial supernatant (PMS). Fractionation of the PMS on sucrose gradients and poly(A+) mRNA detection by hybridization to [3H] poly(U) show that cytoplasmic poly(ADP-ribose) polymerase is exclusively localized in free mRNP. The glycohydrolase activity sedimented mostly in the 6 S region but 1/3 of the activity was in the free mRNP zone. Seven poly(ADP-ribose) protein acceptors were identified in the PMS in the Mr 21,000-120,000 range. The Mr 120,000 protein corresponds to automodified poly(ADP-ribose) polymerase. A Mr 21,000 protein acceptor is abundant in PMS and a Mr 34,000 is exclusively associated with ribosomes and ribosomal subunits. The existence of both poly(ADP-ribose) polymerase and glycohydrolase activities in free mRNP argues in favour of a role of poly(ADP-ribosylation) in mRNP metabolism. A possible involvement of this post translational modification in the mechanisms of repression-derepression of mRNA is discussed.
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PMID:Cytoplasmic poly(ADP-ribose) polymerase and poly(ADP-ribose) glycohydrolase in AEV-transformed chicken erythroblasts. 284 54

The molecular mechanism of activation of Ca2+/Mg2+-dependent endonuclease in thymocytes of irradiated rats was studied. Thymocyte nuclei of control and irradiated rats were pre-incubated with NAD under conditions favourable for poly ADP-ribosylation. Pre-incubation results in a decrease in the rate of autolytic DNA digestion by Ca2+/Mg2+-dependent endonuclease of 6-7- and 2-3-fold for control and irradiated animals, respectively. The activity of Ca2+/Mg2+-nuclease extracted from the nuclei pre-incubated with NAD is also considerably decreased. The presence of nicotinamide and thymidine in the preincubation medium prevents the suppression of Ca2+/Mg2+-nuclease activity. In the experiments performed with isolated nuclei and permeabilized thymocytes the synthesis of poly(ADP-ribose) does not significantly change within 1 h after irradiation at a dose of 10 Gy, whereas 2 and 3 h after the exposure it decreases by 35-40 and 45-55 per cent, respectively. The activity of poly(ADP-ribose) glycohydrolase in this period is similar to that in the controls. The average size of the de novo synthesized chains of poly(ADP-ribose) increases from 11 to 17 ADP-ribose units by the second hour after irradiation. Inhibition of poly(ADP-ribose) polymerase in the postirradiation period preceded the internucleosomal fragmentation of chromatin. The results suggest that activation of Ca2+/Mg2+-nuclease in irradiated thymocytes is accounted for by the disturbance of its poly ADP-ribosylation.
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PMID:Inhibition of poly(ADP-ribose) polymerase as a possible reason for activation of Ca2+/Mg2+-dependent endonuclease in thymocytes of irradiated rats. 312 76

Poly(ADP-ribose) polymerase is a nuclear enzyme that is highly conserved in eucaryotes. Its activity is totally dependent on the presence of DNA containing single or double stranded breaks. We have shown that this activation results in a decondensation of chromatin superstructure in vitro, which is caused mainly by hyper(ADP-ribosy)ation of histone H1. In core particles, the modification of histone H2B leads to a partial dissociation of DNA from core histones. The conformational change of native chromatin by poly(ADP-ribosyl)ation is reversible upon degradation of the histone H1-bound poly(ADP-ribose) by poly(ADP-ribose) glycohydrolase. We propose that cuts produced in vivo on DNA during DNA repair activate poly(ADP-ribose) polymerase, which then synthesizes poly(ADP-ribose) on histone H1, in particular, and contributes to the opening of the 25-nm chromatin fiber, resulting in the increased accessibility of DNA to excision repair enzymes. This mechanism is fast and reversible.
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PMID:Modulation of chromatin structure by poly(ADP-ribosyl)ation. 313 15

Hydrolysis of protein-bound 32P-labelled poly(ADP-ribose) by poly(ADP-ribose) glycohydrolase shows that there is differential accessibility of poly(ADP-ribosyl)ated proteins in chromatin to poly(ADP-ribose) glycohydrolase. The rapid hydrolysis of hyper(ADP-ribosyl)ated forms of histone H1 indicates the absence of an H1 dimer complex of histone molecules. When the pattern of hydrolysis of poly(ADP-ribosyl)ated histones was analyzed it was found that poly(ADP-ribose) attached to histone H2B is more resistant than the polymer attached to histone H1 or H2A or protein A24. Polymer hydrolysis of the acceptors, which had been labelled at high substrate concentrations (greater than or equal to 10 microM), indicate that the only high molecular weight acceptor protein is poly(ADP-ribose) polymerase and that little processing of the enzyme occurs. Finally, electron microscopic evidence shows that hyper(ADP-ribosyl)ated poly(ADP-ribose) polymerase, which is dissociated from its DNA-enzyme complex, binds again to DNA after poly(ADP-ribose) glycohydrolase action.
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PMID:Poly(ADP-ribose) accessibility to poly(ADP-ribose) glycohydrolase activity on poly(ADP-ribosyl)ated nucleosomal proteins. 371

Poly(ADP-ribose) synthetase was identified as the main acceptor of this polymer produced in isolated nuclei of rat liver. When the nuclei were incubated with [32P]NAD at a limited concentration (2.4 microM) and for a brief period (10 s), a protein with Mr = 110,000 was predominantly poly(ADP-ribosyl)ated, as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The modification of this protein increased upon longer incubations or at higher NAD concentrations, and induced a marked increase in the apparent molecular weight. A comparison with poly(ADP-ribose) synthetase (Mr = 110,000) of rat liver under various conditions suggested that the increase in the molecular weight of the acceptor resembled that of the synthetase undergoing multiple auto-poly(ADP-ribosyl)ation. This interpretation was further supported by the following observations: 1) [32P]poly(ADP-ribose) attached to the acceptor co-eluted with the synthetase activity from a hydroxyapatite column; 2) the [32P]poly(ADP-ribose).acceptor complex isolated on the column was converted to a very large complex by further incubation with NAD; and 3) a group of large poly(ADP-ribose).acceptor complexes were reduced to a single molecular species with Mr = 110,000 by extensive digestion with poly(ADP-ribose) glycohydrolase. These findings altogether suggested that poly(ADP-ribose) synthesized in isolated nuclei was principally bound to the synthetase itself.
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PMID:Poly(ADP-ribose) synthetase, a main acceptor of poly(ADP-ribose) in isolated nuclei. 626 Jul 86

Previously it had been shown that poly(ADP-ribose) polymerase requires DNA for its activity and that this enzyme is auto-poly(ADP-ribosyl)ated. The studies reported here indicate that this self-modification inhibits the enzyme and decreases its affinity for DNA, as shown by sucrose gradient density centrifugation. The coupling of poly(ADP-ribose) polymerase with poly(ADP-ribose) glycohydrolase reactivates the polymerase by degrading poly(ADP-ribose) and restoring the polymerase-DNA complex. The assay of polymerase in the presence of glyco-hydrolase was made possible by use of a double-label assay involving release of 14C-labelled nicotinamide and the incorporation of 3H-labelled ADP-ribose from NAD+. These results provide the basis for a shuttle mechanism in which the polymerase can be moved on and off DNA by the action of these two enzymes. Mg2+ and histone H1 appear to activate the polymerase by increasing the affinity of the polymerase for DNA.
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PMID:A shuttle mechanism for DNA-protein interactions. The regulation of poly(ADP-ribose) polymerase. 629 17

The activities of three principal enzymes engaged in the biosynthesis and degradation of poly(adenosine diphosphate-ribose) [poly(ADP-ribose)] were examined in cell nuclei isolated from adenomatous polyps (tubular adenomas of familial polyposis coli, villous adenoma, and tubulovillous adenoma), cancers, and normal mucosa of human colon. The activities of poly(ADP-ribose) synthetase in adenomatous polyps [161 +/- 46 (S.E.) pmol/min/mg DNA] and cancers (114 +/- 32 pmol/min/mg DNA) were, on an average, about 3 and 2 times, respectively, higher than those in normal mucosa (52 +/- 24 pmol/min/mg DNA); the difference was statistically significant (p less than 0.001). The activity of poly(ADP-ribose) glycohydrolase was also significantly high in adenomatous polyps (13.0 +/- 3.4 nmol/min/mg DNA), but not in cancers (10.1 +/- 2.5 nmol/min/mg DNA), compared with normal mucosa (5.2 +/- 1.4 nmol/min/mg DNA) (p less than 0.001). The activity of ADP-ribosyl protein lyase, in contrast, was lower in adenomatous polyps (152 +/- 40 pmol/min/mg DNA) than in normal mucosa (345 +/- 111 pmol/min/mg DNA) and cancers (288 +/- 80 pmol/min/mg DNA) (p less than 0.001). Analyses of reaction products with snake venom phosphodiesterase digestion revealed that poly(ADP-ribose) synthesized in nuclei of normal mucosa, adenomatous polyps, and cancers had the average chain lengths of 2.9, 1.7, and 9.7 ADP-ribose units, respectively. Based upon these values and total amounts of ADP-ribose incorporated, the amount of poly(ADP-ribose) synthesized per mg DNA in 30 min was calculated as 308, 1510, and 106 pmol in the above three types of colon tissues, respectively. These results suggested that a larger amount of monomers and short oligomers of ADP-ribose was synthesized in adenomatous polyps, while a smaller number of longer polymers was produced in cancers as compared with normal mucosa. Immunohistochemical analysis of these tissues using anti-poly(ADP-ribose) antibody supported this view.
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PMID:Aberration of poly(adenosine diphosphate-ribose) metabolism in human colon adenomatous polyps and cancers. 640 58

Poly(ADP-ribose) synthetic activity in isolated nucleoli from rapidly growing mouse ascites tumor cells and ADP-ribosylation of the nucleolar proteins in vitro were studied. The specific activity of the synthesis in the nucleoli was significantly higher than that in the chromatin. The optimum magnesium and NAD+ concentrations, and the effect of RNase treatment on the reaction in the nucleoli were also distinctly different from those in the chromatin. Hydrolysis of the reaction product of the nucleoli with snake venom phosphodiesterase and with calf thymus poly(ADP-ribose) glycohydrolase yielded 5'-AMP and 2'-(5"-phosphoribosyl))5'-AMP, and ADP-ribose, respectively. The average chain length of the polymer formed in the nucleoli was found to be about 4 as a whole, but the distribution was heterogenous, from 1.2 to over 12. Analysis of ADP-ribosylated proteins in the nucleoli by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate revealed that several non-histone proteins with molecular weights of over 100,000 were highly ADP-ribosylated compared with other proteins including histones. This pattern was also different from that of the chromatin. These experimental results demonstrate that the nucleoli are independent from the chromatin as regards poly(ADP-ribose) synthesis in vitro.
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PMID:Poly(ADP-ribose) synthesis in nucleoli and ADP-ribosylation of nucleolar proteins in mouse ascites tumor cells in vitro. 728 63

Adenosine diphosphate (hydroxymethyl)pyrrolidinediol (ADP-HPD), a nitrogen-in-the-ring analog of ADP-ribose, was recently shown to be a potent and specific inhibitor of poly(ADP-ribose) glycohydrolase. Analysis of the inhibition kinetics of the hydrolase by ADP-HPD using the method of Lineweaver and Burk yields a noncompetitive double-reciprocal plot. Both the intercept (1/V) versus [inhibitor] replot and the slope (Km/V) versus [inhibitor] replot are hyperbolic, indicating partial noncompetitive inhibition. Inhibitor dissociation constants Kii = 52 nM and Kis = 80 nM were determined for ADP-HPD by analysis of the intercept versus [inhibitor] and slope versus [inhibitor] replots. These results show that although ADP-HPD is extremely potent in inhibiting poly(ADP-ribose) glycohydrolase, its effectiveness is limited by its partial inhibition. ADP-HPD was significantly less potent as an inhibitor of the NAD glycohydrolase from Bungarus fasciatus venom. Analysis of the inhibition kinetics using the Lineweaver and Burk method indicated that ADP-HPD was a linear-competitive inhibitor of the NAD glycohydrolase with a Ki of 94 microM. The results indicate that at low concentration ADP-HPD will be a selective inhibitor of poly(ADP-ribose) glycohydrolase; however, complete inactivation of the activity will be difficult to obtain.
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PMID:Mechanism of inhibition of poly(ADP-ribose) glycohydrolase by adenosine diphosphate (hydroxymethyl)pyrrolidinediol. 747 61

Oenothein B, a macrocircular dimeric ellagitannin, was found to be a potent and specific inhibitor of poly(ADP-ribose) glycohydrolase. Oenothein B suppressed glucocorticoid-sensitive mouse mammary tumor virus (MMTV) transcription in 34I cells. This suppression was accompanied by inhibition of glucocorticoid-induced endogeneous de-poly(ADP-ribosyl)ation of high mobility group (HMG) 14 and 17 proteins. These results suggest that de-poly(ADP-ribosyl)ation of these proteins may be closely connected with the events initiating glucocorticoid-sensitive MMTV gene transcription.
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PMID:A macrocircular ellagitannin, oenothein B, suppresses mouse mammary tumor gene expression via inhibition of poly(ADP-ribose) glycohydrolase. 775 7


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