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:3.1.30.2 (endonuclease)
18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Synthesis of DNA and poly(adenosine diphosphoribose) [poly(ADPR)] was examined in permeabilized xeroderma pigmentosum lymphoblasts (XP3BE) before and after UV irradiation and in the presence and absence of Micrococcus luteus UV endonuclease. M. luteus UV endonuclease had no effect on the level of DNA or poly(ADPR) synthesis in control, unirradiated cells. UV irradiation caused a decrease in replicative DNA synthesis without any significant change in poly(ADPR) synthesis. In UV-irradiated cells treated with M. luteus UV endonuclease, DNA synthesis was restored to a level slightly greater than in the unirradiated control cells, and poly(ADPR) synthesis increased by 2- to 4-fold. Time--course studies showed that the UV endonuclease dependent poly(ADPR) synthesis preceded the endonuclease-dependent DNA synthesis. Inhibition of endonuclease-dependent poly(ADPR) synthesis with 3-aminobenzamide, 5-methylnicotinamide, or theophylline produced a partial inhibition of the endonuclease-dependent DNA synthesis. Conversely, inhibition of the endonuclease-dependent DNA synthesis with dideoxythymidine triphosphate, phosphonoacetic acid, or aphidicolin had no effect on the endonuclease-dependent poly(ADPR) synthesis. These studies show that stimulation of poly(ADPR) synthesis in UV-irradiated cells occurs subsequent to the DNA strand breaks created by the specific action of the UV endonuclease on UV-irradiated DNA. The effect of the inhibitors of poly(ADPR) synthesis in UV-irradiated cells indicates that the endonuclease-stimulated DNA synthesis is dependent in part on the prior synthesis of poly(ADPR).
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PMID:Poly(adenosine diphosphoribose) synthesis in ultraviolet-irradiated xeroderma pigmentosum cells reconstituted with Micrococcus luteus UV endonuclease. 626 58

Cell survival and induction of endonuclease-sensitive sites in DNA were measured in human fibroblast cells exposed to fluorescent light or germicidal ultraviolet light. Cells from a xeroderma pigmentosum patient were hypersensitive to cell killing by fluorescent light, although less so than for germicidal ultraviolet light. Xeroderma pigmentosum cells were deficient in the removal of fluorescent light-induced endonuclease sites that are probably pyrimidine dimers, and both the xeroderma pigmentosum and normal cells removed these sites with kinetics indistinguishable from those for ultraviolet light-induced sites. A comparison of fluorescent with ultraviolet light data demonstrates that there are markedly fewer pyrimidine dimers per lethal event for fluorescent than for ultraviolet light, suggesting a major role for non-dimer damage in fluorescent light lethality.
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PMID:Fluorescent-light-induced lethality and DNA repair in normal and xeroderma pigmentosum fibroblasts. 626 82

The loss of pyrimidine dimers in nondividing populations of an excision-repair deficient xeroderma pigmentosum group A strain (XP12BE) was measured throughout long periods (up to 5 months) following exposure to low doses of ultraviolet light (UV, 254 nm) using a UV endonuclease-alkaline sedimentation assay. Excision of about 90% of the dimers induced by 1 J/m2 occurred during the first 50 days. The rate curve has some similarities with that of normal excision-repair proficient cultures that may not be coincidental. Rate curves for both XP12BE and normal cultures are characterized by a fast and slow component, with both rate constants for the XP12BE cultures (0.15 day-1 and 0.025 day-1) a factor of 10 smaller than those observed for the respective components of normal cell cultures. The slow components for both XP12BE and normal cultures extrapolate to about 30% of the initial number of dimers. No further excision was detected throughout an additional 90-day period even though the cultures were capable of excision-repair of other newly-introduced pyrimidine dimers. We conclude that nondividing XP12BE cells in addition to having a slower repair rate, cannot repair some of the UV-induced DNA damage. The repair in XP12BE is shown to have biological significance as detected by a cell-survival assay and dose-fractionation techniques. Nondividing XP12BE cells are more resistant to UV when irradiated chronically than when irradiated acutely with the same total dose.
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PMID:Evidence that DNA excision-repair in xeroderma pigmentosum group A is limited but biologically significant. 630 55

Specific excision of thymine dimers from isolated normal human and xeroderma pigmentosum (XP complementation groups A, C, D and G) chromatin was investigated under cell-free conditions. Crude extracts derived from unirradiated XP groups A, C and G cells were unable to excise dimers from their own nuclear sonicates, native chromatin and whole-cell sonicates prepared after exposure to 100 J/m2 of u.v. radiation at 254 nm, while normal-cell extracts were able to do so from all substrates including purified DNA. However, the extracts of XP groups A, C and G cells became capable of excising thymine dimers from chromatin preparations depleted of loosely bound nonhistone proteins with 0.35 M NaCl and from purified DNA. Extracts of XP group D cells catalyzed normal levels of excision from nuclear sonicates, native chromatin and 0.35 M NaCl-treated chromatin. These results suggest that none of the XP groups examined is deficient in a dimer-specific u.v. endonuclease. XP groups A, C and G cells are apparently defective in 'XP factors' present in the non-histone protein fraction, which are required for the excision of thymine dimers from chromatin. The XP group D factor appears to be different from the others. Extracts from XP groups A, C and G cells were able to complement each other with respect to dimer excision from chromatin. Novobiocin (200 micrograms/ml) completely inhibited dimer excision effected by extracts of normal cells or by complementing extracts of XP cells.
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PMID:Defective thymine dimer excision from xeroderma pigmentosum chromatin and its characteristic catalysis by cell-free extracts. 664 Aug 43

Excision repair was measured in normal human and xeroderma pigmentosum group C cells treated with 7,12-dimethylbenz[a]-anthracene 5,6-oxide and with ultraviolet radiation by the techniques of unscheduled DNA synthesis, repair replication, a modification of bromodeoxyuridine photolysis employing the dye Hoechst 33258 and 365 nm radiation, and endonuclease-sensitive sites assay. Radioautography and repair replication showed that in normal cells the magnitude of repair after a saturation dose of epoxide (approx. 10 microM) to be 0.1-0.2 that after a saturating ultraviolet dose (20 J/m2 at 254), though survival data showed that both doses gave nearly similar killings. Repair was of the long-patch type and repair kinetics after the epoxide treatment were similar to ultraviolet. After a combined treatment with both agents, unscheduled synthesis in normal cells was more than additive, although, considering the experimental errors, these data and those of repair replication are consistent with additivity. The epoxide did not inhibit loss of sites sensitive to the ultraviolet endonuclease. However, after a combined treatment to xeroderma pigmentosum cells there was appreciably less unscheduled synthesis than for the sum of both treatments and the epoxide inhibited the loss of nuclease-sensitive sites. We interpret the data to indicate that there are different rate-limiting steps in the removal of the ultraviolet and the epoxide damages, and that the residual repair activity in xeroderma pigmentosum cells is accomplished by different, not just fewer, enzymes than in normal cells.
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PMID:DNA excision repair in human cells treated with ultraviolet radiation and 7,12-dimethylbenz[a]anthracene 5,6-oxide. 677 Sep 2

The mechanism by which mammalian cells replicate DNA containing pyrimidine dimers is poorly understood. When DNA synthesis is initiated after UV-irradiation in bacteria, parental DNA containing pyrimidine dimers has been shown to 'exchange' into the daughter strand DNA by a recA-dependent mechanism. In earlier experiments, when growing mammalian cells were UV-irradiated and then incubated with labelled thymidine, pyrimidine dimers were initially interpreted to be in the newly synthesized DNA, but later were found to be only adjacent to newly synthesized DNA in daughter strand present before UV treatment. A way to avoid these problems of interpretation would be to use cells in G0 or G1 which are not synthesizing DNA at the time of irradiation. UV damage could then be detected in a very sensitive quantitative assay such as that recently described using alkaline elution and an endonuclease preparation from Micrococcus luteus. I have now used this approach and report that up to 3 dimers per 10(9) daltons of daughter strand DNA could be detected 34-45 h after UV-irradiation in human peripheral blood lymphocytes (PBL), normal human fibroblasts, group A xeroderma pigmentosum (XP) fibroblasts and mouse 3T3 cells. This represents approximately 1-3% of the dimers present in the parent strand at this time after UV.
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PMID:Recombination of parent and daughter strand DNA after UV-irradiation in mammalian cells. 687 78

The UV-endonuclease approach to detect DNA damage has been combined with the alkaline elution technique with a resultant marked increase in sensitivity compared to the conventional method using alkaline sedimentation. DNA from UV-irradiated cells was digested on an inert filter with an extract from Micrococcus luteus and then analyzed by alkaline elution. Endonuclease-sensitive sites (endo-sites) were measured after doses of 0.08-0.7 Jm-2 of UV-radiation. An estimate of endo-site production with UV radiation, 0.27 endo-sites/10(8) daltons of DNA/0.1 Jm-2, was similar to that usually seen at higher doses by others. With repair incubation, approx. 50% of the endo-sites were removed in 4 h by normal human fibroblasts after 0.2 or 0.4 Jm-2; no appreciable repair was seen in xeroderma pigmentosum fibroblasts from complementation group A after 24 h of repair incubation. No photoreaction of UV damage due to 0.4 Jm-2 was detected in normal human fibroblasts. The endonuclease preparation also recognized DNA damage produced by ionizing radiation or an alkylating agent. Approx. 0.4 endo-sites/10(8) daltons of DNA were detected after a dose of 1 krad and 1 endo-site/10(8) daltons was observed after exposure of human cells to 2.5 microM MNNG for 1.3 h. The lesions detected after MNNG treatment by the endonuclease preparation decreased with post-treatment incubation--T1/2 8 h. The kinetics of removal of the endo-sites induced by MNNG were similar in normal cells and human cells of the mer- phenotype which has been shown to be more sensitive by cell killing to alkylating-agent damage. This should prove to be a useful approach to study DNA damage and repair since the entire assay can be done in several hours and a very low level of damage (1 endo-site/2 x 10(9) daltons of DNA) can be detected.
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PMID:Measurement of M. luteus endonuclease-sensitive lesions by alkaline elution. 711 Jan 77

Histone acetylation, DNA replicative synthesis, UV-induced DNA repair synthesis, and UV-induced endonuclease-sensitive sites were measured in normal human fibroblasts and xeroderma pigmentosum fibroblasts (complementation groups A, C, and D) following exposure to sodium butyrate. In all four cell types, treatment with millimolar concentrations of sodium butyrate resulted in a hyperacetylation of the core histones. Furthermore, following an exposure of 20 mM sodium butyrate for 48 h, the extent of hyperacetylation was the same in each cell type. In agreement with previous reports, we observed a marked decrease in DNA replicative synthesis in each cell type following increasing times of exposure to sodium butyrate. On the other hand, we observed a marked increase in DNA repair synthesis occurring during early times after UV irradiation in normal cells and in two of the xeroderma pigmentosum cell strains (groups C and D). This increase appeared to correlate with the increase in the highest acetylated form of histone H4. Furthermore, the total number of endonuclease-sensitive sites (i.e. prior to the onset of repair) induced by UV radiation was the same in both butyrated-treated and untreated normal cells over the dose range of 0-20 J/m2. However, the initial rate of removal of these sites increased in butyrate-treated normal cells. These results indicate that sodium butyrate stimulates the initial rate of nucleotide excision repair in both normal and (partially) repair-deficient human cells at concentrations where the histones are maximally hyperacetylated.
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PMID:Sodium butyrate stimulates DNA repair in UV-irradiated normal and xeroderma pigmentosum human fibroblasts. 714 58

DNA-repair characteristics of xeroderma pigmentosum belonging to complementation group F were investigated. The cells exhibited an intermediate level of repair as measured in terms of (1) disappearance of T4 endonuclease-V-susceptible sites from DNA, (2) formation of ultraviolet-induced strand breaks in DNA, and (3) ultraviolet-induced unscheduled DNA synthesis during post-irradiation incubation. The impaired ability of XP3YO to perform unscheduled DNA synthesis was restored, to half the normal level, by the concomitant treatment with T4 endonuclease V and ultraviolet-inactivated Sendai virus. It is suggested that xeroderma pigmentosum cells of group F may be defective, at least in part, in the incision step of excision repair.
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PMID:Repair of ultraviolet radiation damage in xeroderma pigmentosum cells belonging to complementation group F. 720 91

Size separation after UV-endonuclease digestion of DNA from UV-irradiated human cells using denaturing conditions fractionates the genome based on cyclobutane pyrimidine dimer content. We have examined the largest molecules available (50-80 kb; about 5% of the DNA) after fractionation and those of average size (5-15 kb) for content of some specific genes. We find that the largest molecules are not a representative sampling of the genome. Three contiguous genes located in a G+C-rich isochore (tyrosine hydroxylase, insulin, insulin-like growth factor II) have concentrations two to three times greater in the largest molecules. This shows that this genomic region has fewer pyrimidine dimers than most other genomic regions. In contrast, the beta-actin genomic region, which has a similar G+C content, has an equal concentration in both fractions as do the p53 and beta-globin genomic regions, which are A+T-rich. These data show that DNA damage in the form of cyclobutane pyrimidine dimers occurs with different probabilities in specific isochores. Part of the reason may be the relative G+C content, but other factors must play a significant role. We also report that the transcriptionally inactive insulin region is repaired at the genome-overall rate in normal cells and is not repaired in xeroderma pigmentosum complementation group C cells.
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PMID:Identification of a large genomic region in UV-irradiated human cells which has fewer cyclobutane pyrimidine dimers than most genomic regions. 748 Jan 36


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