Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.21.1 (DNase)
7,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The repair mode of DNA replication has been demonstrated in isolated nuclei from UV-irradiated human cells. Nuclei are incubated in a mixture containing [(3)H]thymidine triphosphate and bromodeoxyuridine triphosphate in a 1:5 ratio. The (3)H at the density of parental DNA in alkaline CsCl density gradients is then a measure of repair. In nuclei prepared from WI38 cells 30 min after irradiation, repair replication is UV dependent and proceeds at approximately the in vivo rate for 5 min. Repair replication is reduced in irradiated nuclei or in nuclei prepared immediately after irradiation. It is Mg(2+)-dependent and stimulated by added ATP and deoxyribonucleoside triphosphates. No repair replication is observed in nuclei from xeroderma pigmentosum (complementation group A) cells. However, upon addition of coliphage T4 endonuclease V, which specifically nicks DNA containing pyrimidine dimers, repair replication is observed in nuclei from irradiated xeroderma pigmentosum cells and is stimulated in WI38 nuclei. The reaction then persists for an hour and is dependent upon added ATP and deoxyribonucleoside triphosphates. The repair label is in stretches of roughly 35 nucleotides, as it is in intact cells. Added pancreatic DNase does not promote UV-dependent repair synthesis. Our results support the view that xeroderma pigmentosum (group A) cells are defective in the incision step of the DNA excision repair pathway, and demonstrate the utility of this system for probing DNA repair mechanisms.
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PMID:Phage T4 endonuclease V stimulates DNA repair replication in isolated nuclei from ultraviolet-irradiated human cells, including xeroderma pigmentosum fibroblasts. 27 29

Apurinic DNA endonuclease activity from cultured human fibroblasts was resolved into two species by phosphocellulose chromatography. The species had sedimentation coefficients of 3.3 S and 2.8 S and apparent Km's for apurinic sites of 5 and 44 nM, respectively. The low Km species was absent from extracts of cell lines XP5BE, XP6BE and XP7BE of xeroderma pigmentosum complementation group D.
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PMID:Xeroderma pigmentosum fibroblasts of the D group lack an apurinic DNA endonuclease species with a low apparent Km. 64 22

Endonuclease activity upon depurinated DNA was measured in extracts of cultured fibroblasts from xeroderma pigmentosum patients. Cell lines from complementation groups A, B, C, E, and the XP-variant had slightly reduced levels of activity, but cell lines from complementation group D had one-sixth of the normal activity. An altered pH dependence and a higher apparent Km for substrate in D-cell lines indicate that the remaining activity is also qualitatively different from the activity found in normal cells. A higher Km was also found in cell lines from the A-complementation group but not in cell lines from the C-complementation group. These defects in apurinic DNase might account for the neurological disorders in patients from the D- and the A-complementation groups.
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PMID:An altered apurinic DNA endonuclease activity in group A and group D xeroderma pigmentosum fibroblasts. 106 98

A DNA endonuclease complex which recognizes predominantly pyrimidine dimers in UVC irradiated DNA has been isolated from the chromatin of normal human and xeroderma pigmentosum, complementation group D (XPD) lymphoblastoid cells. The activity of the normal complex on UVC irradiated DNA was increased approximately 2.5 and 1.5 fold over activity on damaged naked DNA, when core (histones H2A, H2B, H3, H4) and total (core+histone H1) nucleosomal DNA, respectively, was used. In contrast, the XPD complex showed no increase in activity on UVC irradiated total and only a 1.4 fold increase on UVC irradiated core nucleosomal DNA, indicating that the XPD complex is defective in its ability to incise UVC irradiated nucleosomal DNA. The normal complex was able to correct this defect in the XPD complex at the nucleosomal level.
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PMID:Isolation of a DNA endonuclease complex in XPD cells which is defective in ability to incise nucleosomal DNA containing pyrimidine dimers. 147 50

Human hereditary diseases such as xeroderma pigmentosum, Fanconi's anemia, ataxia telangiectasia, and Bloom's syndrome are characterized by a proneness for developing cancer associated with abnormalities in the processing of DNA damage. The molecular defects responsible for predisposing human tissues to cancer are still not well understood, despite the fact that a considerable amount of work has already been done on this problem. In this paper, we show that in human tumor cell lines, in cells transformed by DNA tumor viruses, and in cells derived from certain cancer-prone disorders, the level of activity of a 42-kDa deoxyribonuclease is many times higher than in diploid untransformed control cells. This suggests that this activity is linked to, or may play a role in, malignant transformation.
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PMID:Enhanced deoxyribonuclease activity in human transformed cells and in Bloom's syndrome cells. 280 19

The damage-directed strand incision step in the nucleotidyl DNA excision-repair pathway (NDERP) was characterized in quiescent monolayer cultures of human fibroblasts in which the plasma membrane was selectively permeabilized with saponin. When permeable normal human fibroblasts (NHF) were incubated in a DNA-repair assay mixture lacking the deoxyribonucleoside triphosphate precursors, the numbers of UV-dependent DNA-strand breaks were increased by about 9-fold consistent with the uncoupling of incision from gap-filling DNA synthesis and ligation. In uncoupled NHF omission of ATP reduced the numbers of UV-dependent strand breaks by 84% confirming the requirement for ATP for reparative strand incision. Time-course experiments indicated that the maximum rate of strand incision occurred in the first 10 min of incubation of permeable cells and diminished to 16-28% of this rate between 30 and 60 min of incubation. The initial rate of incision in permeable NHF was estimated to be 20% of that seen in intact fibroblasts. Dose-response studies indicated an initial saturation of strand incision activity at fluences between 10 and 25 J/m2. In permeable group A xeroderma pigmentosum fibroblasts (XPA) few UV-dependent incisions were produced after 10-25 J/m2. In the xeroderma pigmentosum variant (XPV) strain that we studied, strand incisions saturated at a plateau level that was about twice that seen in the NHF strain suggesting the preservation of a higher level of incision activity after permeabilization. After fluences above 50 J/m2 additional strand incision was observed in all cell strains reflecting the activity of a damage-dependent endodeoxyribonuclease that is independent of the NDERP. Saponin-treated fibroblasts were also permeable to pancreatic deoxyribonuclease I and the UV-DNA endonuclease from M. luteus indicating that these preparations may be used for in vitro complementation.
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PMID:Reparative strand incision in saponin-permeabilized human fibroblasts. 367 Mar 27

Irradiation of dominant marker DNA with UV light (150 to 1,000 J/m2) was found to stimulate the transformation of human cells by this marker from two- to more than fourfold. This phenomenon is also displayed by xeroderma pigmentosum cells (complementation groups A and F), which are deficient in the excision repair of UV-induced pyrimidine dimers in the DNA. Also, exposure to UV of the transfected (xeroderma pigmentosum) cells enhanced the transfection efficiency. Removal of the pyrimidine dimers from the DNA by photoreactivating enzyme before transfection completely abolished the stimulatory effect, indicating that dimer lesions are mainly responsible for the observed enhancement. A similar stimulation of the transformation efficiency is exerted by 2-acetoxy-2-acetylaminofluorene modification of the DNA. No stimulation was found after damaging vector DNA by treatment with DNase or gamma rays. These findings suggest that lesions which are targets for the excision repair pathway induce the increase in transformation frequency. The stimulation was found to be independent of sequence homology between the irradiated DNA and the host chromosomal DNA. Therefore, the increase of the transformation frequency is not caused by a mechanism inducing homologous recombination between these two DNAs. UV treatment of DNA before transfection did not have a significant effect on the amount of DNA integrated into the xeroderma pigmentosum genome.
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PMID:UV stimulation of DNA-mediated transformation of human cells. 399 Jun 93

We have determined the levels of DNA polymerase, DNA ligase, a DNase acting on single-stranded DNA, an endonuclease making single-strand breaks in double - stranded DNA and polynucleotide kinase in fibroblasts obtained from nine normal persons and from nine patients with Xeroderma Pigmentosum; the pathological lines belong to the different described clinical forms and to the three different complementation groups described so far. All the enzymes are present in the normal lines and in the Xeroderma lines. The levels are quite variable, but the values obtained in the pathological lines lie within the ones observed in the normal population.
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PMID:Levels of some enzymes acting on DNA in xeroderma pigmentosum. 441 76

DNA endonuclease activities from nuclear proteins of normal human and xeroderma pigmentosum (XP), complementation group A, lymphoblastoid and Cloudman mouse melanoma cells were examined against partially apurinic/apyrimidinic (AP) DNA. Non-histone chromatin-associated and nucleoplasmic proteins, obtained from isolated nuclei, were subfractionated by isoelectric focusing and assayed for DNA endonuclease activity against linear, calf thymus DNA. All of the nine chromatin-associated and three of the nucleoplasmic fractions, which lacked DNA exonuclease activity, were tested for DNA endonuclease activity against both native and partially AP, circular, duplex, supercoiled PM2 DNA. In all three cell lines, four chromatin-associated, but none of the nucleoplasmic fractions, showed increased activity against DNA rendered AP by either heat/acid treatment or by alkylation with methyl methanesulfonate (MMS) followed by heat. One chromatin-associated activity, with pI 9.8, which was not active on native DNA, showed the greatest activity on AP DNA. AP activity was moderately decreased in XP cells and slightly decreased in mouse melanoma cells, as compared with normal cells, in the fraction at pI 9.8. Little or no increased activity was observed in any of the endonucleases from any of the cell lines on MMS alkylated DNA.
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PMID:Nuclear DNA endonuclease activities on partially apurinic/apyrimidinic DNA in normal human and xeroderma pigmentosum lymphoblastoid and mouse melanoma cells. 622 42

Biochemically active human DNA repair protein, xeroderma pigmentosum G (XPG), was overexpressed in insect cells by a recombinant baculovirus. The recombinant baculovirus produced XPG with a mobility of approximately 185 kDa in a denaturing polyacrylamide gel. Indirect immunofluorescence studies demonstrated that the recombinant full-length XPG protein was expressed predominantly as a nuclear protein. The recombinant XPG protein was purified to apparent homogeneity using Q-sepharose, S-300 size exclusion, and Mono Q column chromatography. XPG protein showed a structure-specific DNA endonuclease activity, and a preferential affinity to single-stranded DNA and RNA compared to double-stranded DNA.
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PMID:XPG protein has a structure-specific endonuclease activity. 765 64


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