Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.21.1 (DNase)
 7,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using eukaryotic cells that have been rendered permeable to exogenously supplied nucleotides, we have characterized the activity of the poly(adenosine diphosphoribose) (poly(ADPR)) synthesis system and compared it to the DNA synthesis complex. The synthesis of poly(ADPR) is dependent on the presence of NAD and Mg2+. It does not require ATP, NaF or a monovalent cation. It is inhibited by N-ethylmaleimide. The reaction product conforms to the nuclease susceptibilities expected for poly(ADP ribose) in that it is degraded by venom phosphodiesterase but not by DNAase of RNAase. A comparison of the effects of inhibitors of poly(ADPR) synthesis and DNA synthesis clearly distinguishes between the two enzymatic systems. Nicotinamide, 5-methyl nicotinamide, thymidine, 5-bromo deoxyuridine, adenosine diphosphoribose, caffeine and formycin all inhibit poly(ADPR) synthesis but not DNA synthesis. In contrast, araCTP, cytembena and phosphonoacetic acid all inhibit DNA synthesis but not poly(ADPR) synthesis. Addition of DNAase to the permeable cells causes a marked stimulation of poly(ADPR) synthesis. L cells in logarithmic growth were found to have high levels of activity of the DNA synthesis complex and low levels of activity of the poly(ADPR) synthesis system. In contrast, cells at plateau phase density demonstrate a decrease in the activity of the DNA synthesis complex and a marked increase in activity of the poly(ADPR) synthesis system. When examined in the presence of added DNAase, the activity of the poly(ADPR) synthesis system is the same in cells obtained from log or plateau phase cultures. This indicates that the physiologic activity of the enzyme varies while the total amount of enzyme remains constant. When the permeable cells are allowed to synthesize both poly(ADPR) and DNA simultaneously, the synthesis of one polymer has no effect on the rate of synthesis of the other.
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PMID:Characterization and comparison of poly(adenosine dephosphoribose) synthesis and DNA synthesis in nucleotide-permeable cells. 20 14

Treatment of growing cultures of Mycobacterium smegmatis with alkylating agents (methyl methanesulphonate, ethyl methanesulphonate, nitrogen mustard, or mitomycin C) or with ultraviolet light resulted in enhanced specific activities of a DNA polymerase and of an ATP-dependent deoxyribonuclease. Similar results had previously been obtained with hydroxyurea and with iron limitation. The three of these treatments which were tested (methyl methanesulphonate, mitomycin C and hydroxyurea) produced strand breaks or alkali-labile regions in the DNA of this organism. The increased enzyme activities could be prevented by simultaneous treatment with inhibitors of protein synthesis. In contrast, treatment of the cultures with intercalating agents (ethidium bromide, acridine orange, or proflavine), 5-fluorouracil, caffeine, or nalidixic acid, inhibited DNA synthesis without increasing the enzyme activities. These treatments did not produce strand breaks in the DNA of this organism. The results support the hypothesis that, in M. smegmatis, damage to DNA induces increased synthesis of enzymes associated with DNA repair.
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PMID:Increased DNA polymerase and ATP-dependent deoxyribonuclease activities following DNA damages in mycobacterium smegmatis. 84 85

Chicken embryo cells were treated with caffeine (0.5-8.0 mM) alone or combined with various chemical and physical DNA-and/or chromatin-interactive agents. Analytical procedures comprised scheduled (SDS) and unscheduled (UDS) DNA synthesis, RNA synthesis (RNS), the activities of O6-alkylguanine-DNA alkyltransferase (AT) and poly (ADP-ribose) polymerase (PARP) as well as nucleoid sedimentation. Additional investigations were done in rat thymic and splenic cells. The effect of caffeine on DNase-I activity served as an in vitro-model system. When present in the PARP-, SDS-, UDS- and RNS-assays, caffeine inhibited the corresponding tracer (14C-NAD, dT-3H, 3H-U) incorporation in a dose-dependent manner. The AT activity was slightly stimulated. At concentrations of 0.06-0.3 mM, caffeine inhibited DNase-I activity by excess substrate. No specific effects of caffeine could be shown by nucleoid sedimentation. Besides the reduced permeability of the cells to nucleic acid precursors, the results obtained with the PARP- and DNase-I assays give evidence for the formation of a DNA-caffeine adduct as a prominent mechanism of cellular caffeine effects including DNA repair inhibition.
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PMID:Caffeine-DNA interactions: biochemical investigations comprising DNA-repair enzymes and nucleic acid synthesis. 930 78