Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.1 (S1 nuclease)
 3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HL-60 cells have an elevated level of cellular myc RNA due to an amplified c-myc gene. Subsequent to chemically induced differentiation of HL-60 cells, both cellular myc RNA levels (Grosso, L. E., and Pitot, H. C., Biochem. Biophys. Res. Commun., 119: 473, 1984) and myc-specific transcription decrease (Grosso, L. E., and Pitot, H. C., Cancer Res., 45: 847-850, 1985). We have compared the primary DNA structure, DNA methylation, and S1 nuclease sensitivity of the myc protooncogene in HL-60 cells before and after chemically induced differentiation. We find no change in the structure or methylation of the c-myc gene. The protooncogene is hypomethylated at CCGG sequences in the 5' region but is extensively methylated at sites detected by sequences homologous to the 3' exon or 3' flanking sequences. Four S1 nuclease-sensitive sites are detected prior to differentiation. After the induction of either myeloid or monocytic differentiation, three of the S1 nuclease-sensitive sites are present. The presence of the fourth S1 nuclease-sensitive site correlates with the transcriptional activity of this gene.
Cancer Res 1985 Oct
PMID:Chromatin structure of the c-myc gene in HL-60 cells during alterations of transcriptional activity. 386 Dec 42

Nucleosomal DNA isolated from bleomycin-treated nuclei shows retarded electrophoretic mobility in neutral gels as compared with the sample isolated from micrococcal (or endogenous) nuclease-digested nuclei. The retardation in electrophoretic mobility is probably due to the presence of single-strand regions in the DNA duplex of bleomycin-treated samples as determined by single-strand-specific S1 nuclease digestion and buoyant density measurements. This observation argues against the possibility that the generation of nucleosomal DNA following drug treatment of nuclei is due to an activation of endogenous nuclease by bleomycin and strongly suggests that the drug has a unique feature of action on chromatin.
Cancer Res 1981 Jun
PMID:Altered gel electrophoretic mobility of bleomycin-mediated release of nucleosomal DNA. 616 61

Single-stranded complementary DNA (cDNA) of the RNA of Gazdar murine sarcoma virus, Gz-MSV/MuLV; Moloney murine leukemia virus, M-MuLV; mouse mammary tumor virus, MMTV; and simian sarcoma virus, SSV-1, were synthesized in endogenous reverse transcriptase reaction. Gz-MSV/MuLV cDNA was also synthesized in exogenous in vitro reverse transcriptase reactions. In the endogenous reaction, 30-35S, or 6.0- to 7.9-kilobase-length cDNA transcripts were synthesized in high yield. In comparison, transcripts synthesized in exogenous reactions were 6.7S, or 0.39 kilobases. The complementarity of the transcripts was verified by both RNA/DNA hybridization and protection studies. dG and dC sequences were detected in 50-77% of the cDNA molecules by affinity chromatography, by annealing and masking studies, and by resistance to S1 nuclease. dT and dA sequences were not detected in the transcripts. These findings are discussed in relation to the possible selective blocking of transcription of retrovirus genes without interfering significantly with the transcription of cellular genes.
Cancer Detect Prev 1981
PMID:Complementary DNA copies of leukemia and sarcoma virus RNA contain sequences of deoxycytidylate and deoxyguanylate. 629 64

The E2a region of the Ad2 genome encodes the Ad2-specific DBP. An inverse correlation between the level of DNA methylation at the 5'-CC*GG-3' sites of the E2a region and the extent of expression of DBP has been demonstrated in Ad2-transformed hamster cell lines (Vardimon et al. 1980). Four different leaders are used in the transcription of the E2a region in cells productively infected with Ad2. The leader located at coordinate 75 on the viral genome is used early after infection and the other three leaders are used late after infection (Chow et al. 1979). The analysis of the integration patterns of the viral DNA in the Ad2-transformed cell lines has revealed that the early leader is deleted in the cell lines which do not express the DBP (Vardimon and Doerfler 1981). The late leader located at coordinate 72 on the viral genome is present. The region encoding that late leader has been subcloned, and the cytoplasmic RNA from the cell line which expresses the DBP has been analyzed. It has been shown that the late leader is used in transformed cells. Hence the absence of the early leader cannot be the immediate reason for the lack of expression of the DBP. Correlations between DNA methylation and the absence of gene expression may indicate that methylation regulates gene expression or that methylation is the consequence of lacking gene expression. In order to decide between these alternatives an in vitro system has been employed. The HindIII A fragment of the Ad2 DNA which encodes the DBP has been methylated in vitro by the HpaII DNA methyltransferase. Methylated or unmethylated HindIII A fragment has been microinjected into the nuclei of Xenopus laevis oocytes. Unmethylated HindIII A fragment has been found to be expressed as specific viral RNA, whereas no viral RNA can be found in oocytes microinjected with methylated HindIII A fragment. The possibility of a nonspecific inhibitory factor in the methylated DNA preparation has been ruled out by the simultaneous microinjection of sea urchin histone gene DNA together with the methylated HindIII A fragment. Histone genes are expressed, while the expression of the methylated viral gene is blocked. By using the single-strand-specific endonuclease S1 we have shown that in Xenopus laevis oocytes initiation of transcription of the E2a region starts exactly at the same site as in Ad2 productively infected cells. These results provide direct evidence for the notion that DNA methylation at specific sites is involved in the regulation of gene expression.
Recent Results Cancer Res 1983
PMID:Can DNA methylation regulate gene expression? 630 51

Structural analysis by chromatography on benzoylated-DEAE-cellulose (BD-cellulose) has been made of hepatic DNA from rats treated for up to 21 weeks with dimethylnitrosamine (DMN). The carcinogen (1 mg/kg body wt) was administered on a daily basis by intraperitoneal injection. By comparison with preparations from saline-treated controls, the proportion of DNA retained by benzoylated-DEAE-cellulose in the presence of 1.0 M NaCl was increased by administration of the carcinogen. Variation in the result, dependent upon the time after the final dose, suggested a complex relationship between structural damage to DNA and duration of treatment. Structural damage was confirmed by S1 nuclease digestion. The observations imply that in the course of chronic administration, increasing time is required to complete DNA repair processes operative in rat liver.
Cancer Lett 1983 Aug
PMID:Transient structural change in hepatic DNA of rats chronically exposed to dimethylnitrosamine. 631 66

We have examined aspects of the interaction of cycled microtubule protein preparations with 35S-labeled mouse DNA tracer in a competition system with unlabelled competitor E. coli or mouse DNA. The nitrocellulose filter binding assay was used to measure interaction by scintillation counting. DNA molecular weight affected the levels of filter retained 35S-labelled mouse tracer DNA. Filter retention levels increased if 35S-labelled mouse DNA tracer size was increased, and the filter binding level decreased if competitor DNA size was increased. There was a sizeable, reproducible difference in the 35S-labelled mouse DNA tracer binding level of about 1% when E. coli or mouse DNA competitors were compared. Mouse DNA more effectively competed with 35S-labelled mouse DNA for microtubule protein binding than did E. coli DNA, suggesting that a small class of higher-organism DNA sequences interacts very strongly with microtubule protein. From other studies we know this to be the MAP fraction (Marx, K.A. and Denial, T. (1984) in The Molecular Basis of Cancer (Rein, R., ed.), Alan R. Liss, New York, in the press; and Villasante, E., Corces, V.G., Manso-Martinez, R. and Avila, J. (1981) Nucleic Acids Res. 9, 895-908). We find that this difference in competitor DNA strength is qualitatively similar under high-stringency conditions (0.5 M NaCl, high competitor [DNA]) we developed for examining high-affinity complexes. Under high-stringency conditions we isolated 1.2% and 0.6% of 35S-labelled mouse DNA at 4200 and 350 bp respective sizes as nitrocellulose filter bound DNA-protein complexes. At both molecular weights these high-affinity DNA sequences, isolated from the filters, were shown to be significantly enriched in repetitive DNA sequences by S1 nuclease solution reassociation kinetics. The kinetics are consistent with about a 4-fold mouse satellite DNA enrichment as well as enrichment in other repetitious DNA sequence classes. The high molecular weight filter-bound DNA samples were sedimented to equilibrium in CsCl buoyant density gradients and found to contain primarily mouse satellite DNA density sequences (1.691 g/cm3) with some minor fractions at other density positions (1.670, 1.682, 1.705, 1.740, 1.760 g/cm3) similar to those observed by our laboratory in previous investigations of micrococcal nuclease-resistant chromatin (Marx, K.A. (1977) Biochem. Biophys. Res. Commun. 78, 777-784). That the high-affinity microtubule-bound DNA was some 3-5-fold enriched in mouse satellite sequences was demonstrated by its characteristic BstNI restriction enzyme cleavage pattern.
 ...
PMID:High-affinity microtubule protein-higher organism DNA complexes. Many-fold enrichment in repetitive mouse DNA sequences comprised of satellite DNAs. 639 51

CC-1065 (NSC 298223), a potent new antitumor antibiotic produced by Streptomyces zelensis, interacts strongly with double-stranded DNA and appears to exert its cytotoxic effects through disruption of DNA synthesis. We undertook this study to elucidate the sites and mechanisms of CC-1065 interaction with DNA. The binding of CC-1065 to synthetic and native DNA was examined by differential circular dichroism or by Sephadex chromatography with photometric detection. The binding of CC-1065 with calf thymus DNA was rapid, being complete within 2 hr, and saturated at 1 drug per 7 to 11 base pairs. The interaction of CC-1065 with synthetic DNA polymers indicated a specificity for adenine- and thymine-rich sites. Agarose gel electrophoresis of CC-1065-treated supercoiled DNA showed that CC-1065 did not intercalate. Site exclusion studies using substitutions in the DNA grooves showed CC-1065 to bind primarily in the minor groove. CC-1065 did not cause DNA breaks; it inhibited susceptibility of DNA to nuclease S1 digestion. It raised the thermal melting temperature of DNA, and it inhibited the ethidium-induced unwinding of DNA. Thus, in contrast to many antitumor agents, CC-1065 stabilized the DNA helix. DNA helix overstabilization may be relevant to the mechanism of action of CC-1065.
Cancer Res 1982 Jul
PMID:Mechanism of interaction of CC-1065 (NSC 298223) with DNA. 708 73

cis-Diamminedichloroplatinum(II) was found to bind to covalently closed circular supercoiled, covalently closed circular nonsupercoiled, and single-strand broken relaxed PM2 DNA and induce different types of DNA conformational changes. Using Kleinschmidt's technique, it was found that binding of cis-diamminedichloroplatinum(II) decreased the DNA length to 75% of the original single-strand broken relaxed DNA without inducing superhelical conformational changes. cis-Diamminedichloroplatinum(II) also shortened the length of covalently closed circular nonsupercoiled DNA before a supercoiled conformation was generated. Single strand-specific nucleases were used to detect drug-induced DNA structural alterations. Local single-strand regions or regions of denaturation were detected by S1 nuclease from Aspergillus oryzae and by BAL-31 nuclease from Alteromonas espejiana BAL-31. The single-strand regions or local denaturation regions do not seem to be related to or caused by DNA superhelical conformational changes since they were detected at drug concentrations at which no significant DNA superhelical turns were found. DNA shortening, superhelical conformational changes, and local denaturation regions can be explained by the previously proposed "DNA intrastrand cross-linking" model (Stone et al., J. Mol. Biol., 104: 793-801, 1976).
Cancer Res 1981 Oct
PMID:DNA supercoiling, shortening, and induction of single-strand regions by cis-diamminedichloroplatinum(II). 719 92

The techniques of viscoelastometry and S1 nuclease digestion were applied to the analysis of DNA damage in rat 9L cells treated with nitrogen mustard and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Results of the S1 nuclease assay permitted quantitation of the amount of single-strand (or alkali-labile) break formation as well as DNA interstrand cross-link formation. In the presence of 2% detergent, only cells treated with nitrogen mustard showed evidence of DNA cross-link formation as determined by this assay. Viscoelastic analysis of cell lysates under denaturing conditions (pH 12.15) showed that cells treated with nitrogen mustard led to substantial increases in both the viscoelastic retardation time and recoil, consistent with the presence of DNA cross-links, while treatment with BCNU led to decreases in these two properties, consistent with the induction of single-strand breaks. Viscoelastic analysis of cell lysates under nondenaturing conditions (pH 11.15) showed that nitrogen mustard produced an increase in retardation time, consistent with single-strand break induction, along with a fast recoiling component that eventually led to gel-like behavior, suggesting the possibility of drug-induced intermolecular DNA-DNA cross-links. BCNU treatment resulted in a decrease in retardation time. This decrease in consistent with induction of DNA interstrand cross-links by BCNU and shows that the single-strand breaks observed at denaturing conditions were due to the presence of alkali-labile sites rather than true strand breaks. While other methods using denaturing conditions have resulted in evidence for DNA cross-links following BCNU treatment, both viscoelastic and S1 nuclease experiments showed negative results in this regard. Further work is needed to clarify this point.
Cancer Res 1980 Sep
PMID:DNA damage in rat 9L cells treated with nitrogen mustard and 1,3-bis(2-chloroethyl)-1-nitrosourea assayed by viscoelastometry and S1 nuclease. 742 37

Photoactivated 8-methoxypsoralen (8-MOP) has been proven to be clinically effective for a number of dermatological conditions including lichen planus, mycosis fungoides, and psoriasis. 8-MOP forms two types of covalent photoproducts with DNA, monoadducts, and bifunctional adducts which cross-link the two DNA strands. Angelicin is a congener of 8-MOP which forms only monoadducts. We have used the combined density and isotopic labeling technique to study repair replication in cultured human fibroblasts treated with either of these compounds and exposed to near-ultraviolet light. In human diploid fibroblasts (WI-38), the time course of repair replication for both compounds is similar. Drug concentration and ultraviolet dose responses are also similar for 8-MOP and angelicin. No repair replication was stimulated by either compound in xeroderma pigmentosum cells from Complementation Group A (XP12BE). These results suggest that repair replication in response to 8-MOP is primarily a response to monoadducts and that the enzymatic pathway for this repair synthesis shares at least one step with the pathway for repair of pyrimidine dimers. Cross-link persistence in treated cells was assayed by use of the single-strand-specific S1 nuclease to digest DNA that did not renature readily following heat denaturation. Partial removal of cross-links was observed in normal, xeroderma pigmentosum variant, and Fanconi's anemia fibroblasts, but not in xeroderma pigmentosum Group A cells.
Cancer Res 1980 Mar
PMID:DNA repair in human cells containing photoadducts of 8-methoxypsoralen or angelicin. 747 Oct 88


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