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

---

Query: EC:2.7.7.7 (DNA polymerase)
17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Helenalin and bis(helenalinyl)malonate were shown to be cytotoxic against the growth of human KB carcinoma cells. DNA synthesis was inhibited significantly. This inhibition was afforded because of the drugs' effects on a number of enzyme activities. The inhibition of IMP dehydrogenase and ribonucleotide reductase complex activities correlated positively with the inhibition of DNA synthesis of the KB cells. DNA polymerase activity was inhibited by the drugs to a lesser degree. The deoxyribonucleotide pools were markedly reduced in the presence of the drug, which would be consistent with a blockage of the enzyme ribonucleotide reductase as well as suppression of DNA synthesis. XMP levels were also reduced, which is consistent with suppression of IMP dehydrogenase activity by the drugs. Ribonucleoside phosphate pools, particularly CDP and GDP, were elevated after drug treatment, which would be expected with a blockage at ribonucleotide reductase. Thus DNA alkylation is not the mechanism of action of the antineoplastic sesquiterpene lactones; rather, the cell-killing effect is related to DNA synthesis inhibition by the drug.
...
PMID:Effect of helenalin and bis(helenalinyl)malonate on nucleic acid and protein synthesis in human KB carcinoma cells. 290 84

In tissues obtained from patients undergoing gastrectomy, the activities of 12 enzymes involved in pyrimidine nucleotide synthesis: cytidine triphosphate (CTP) synthetase, deoxycytidine monophosphate (dCMP) deaminase, thymidine monophosphate (dTMP) kinase, uridine (Urd), deoxycytidine (dCyd) and thymidine (dThd) kinases, Urd, deoxyuridine (dUrd) and dThd phosphorylases, cytidine (Cyd) and dCyd deaminases, and DNA polymerase were examined in the eight-well-differentiated and 12 poorly differentiated gastric cancer tissues and the ten normal tissues. These cases were clinically advanced and serosal invasions were evident. Activities of these enzymes were higher in the poorly differentiated tissues than the well differentiated type and in the normal tissues. Significant differences were noted between the poorly differentiated and well-differentiated types, in dTMP kinase (P less than 0.02), dThd kinase (P less than 0.05), dThd phosphorylase (P less than 0.01), and DNA polymerase (P less than 0.05). The authors' findings show that the level of pyrimidine nucleotide synthesis, in both de novo and salvage pathways, is higher in the poorly differentiated gastric cancer tissues than in the well-differentiated type and suggest that antitumor drugs have an increased susceptibility in cases of poorly differentiated gastric carcinoma.
...
PMID:Pyrimidine nucleotide synthesis is more extensive in poorly differentiated than in well-differentiated human gastric carcinoma. 291 Apr 29

A heat-labile Epstein-Barr virus-specific DNA polymerase stimulatory protein having a molecular mass of 45 kDa was purified from phorbol 12-myristate 13-acetate-treated P3HR-1 cells by column chromatography. The virus DNA polymerase stimulatory protein was precipitated by sera from patients with nasopharyngeal carcinoma but not by sera from healthy donors. The interaction of the stimulatory protein with DNA polymerase was stoichiometric. Furthermore, this protein stimulated Epstein-Barr virus DNA polymerase but not herpes simplex virus type 1 or type 2 or human DNA polymerase alpha. The stimulatory protein did not alter the Km value of dTTP or DNA but did increase the Vmax of DNA polymerase. Salt concentrations between 100 mM and 150 mM KCl were optimal for this protein-induced stimulation of Epstein-Barr virus DNA polymerase activity. The presence of the stimulatory protein in the reaction mixture enhanced the sensitivity of virus DNA polymerase to phosphonoformate.
...
PMID:Demonstration of a stimulatory protein for virus-specified DNA polymerase in phorbol ester-treated Epstein-Barr virus-carrying cells. 299 45

Epstein-Barr virus (EBV) has been found to be associated with nasopharyngeal carcinoma (NPC), and antibodies with high frequency and titer to EBV proteins have been found in sera from NPC patients. Raji cells, an EBV genome-carrying nonproducer cell line, treated with 12-O-tetradecanoylphorbol-13-acetate and n-butyrate induced a unique EBV DNA polymerase which has properties similar to the EBV DNA polymerase induced by 12-O-tetradecanoylphorbol-13-acetate in P3HR-1 cells, an EBV producer cell line. The possible presence of antibodies to this EBV DNA polymerase in NPC patient serum was examined. The mean number of EBV DNA polymerase units neutralized was 380 +/- 168 units/ml serum (mean +/- SD) in 48 sera from patients with NPC, whereas that in the sera from 52 healthy donors was 62 +/- 56 units/ml (p less than 0.01). The EBV DNA polymerase antibody was found to be associated with the immunoglobulin G but not the immunoglobulin A fraction, and its titer was not correlated with the titers against EBV DNase or virus capsid antigen-immunoglobulin A. Whether the EBV DNA polymerase antibody is against the EBV DNA polymerase core protein or its stimulating protein is still being investigated. This study demonstrated the high frequency and high titer of antibody against EBV DNA polymerase in serum from NPC patients and suggested the potential of utilizing this antibody titer to complement other methods for the early diagnosis or prognosis of NPC.
...
PMID:Demonstration of Epstein-Barr virus-specific DNA polymerase in chemically induced Raji cells and its antibody in serum from patients with nasopharyngeal carcinoma. 301 19

The effect of alpha-1-antichymotrypsin (ACT), which is known as an efficient serum protease inhibitor and is detected in tumor cell nuclei, on DNA synthesis was studied. ACT inhibited the activity of DNA polymerase alpha purified from human stomach adenocarcinoma. Other human serum proteins including serum albumin, alpha-1-acidglycoprotein, alpha-1-antitrypsin, and immunoglobulin G, as well as other protease inhibitors, such as leupeptin, pepstatin, PMSF and chymostatin, did not affect the activity of DNA polymerase alpha. It was therefore concluded that the inhibitory action of ACT on DNA polymerase alpha was direct phenomenon unrelated to its protease inhibitory activity. Furthermore, the effect of ACT on DNA synthesis was also studied using lysolecithin-permeabilized cultured human stomach carcinoma cells. ACT added in the medium inhibited DNA synthesis and the degree of inhibition depended on incubation time. It was proportional to ACT concentration and the concentration of ACT required for 50% inhibition was 0.8 mg/ml.
...
PMID:Inhibition of DNA synthesis by alpha-1-antichymotrypsin. 327 75

The distribution of DNA polymerase alpha-positive cells in neoplasia of the uterine cervix and in normal cervical epithelium was studied using a monoclonal antibody against DNA polymerase alpha. The positive cells were found only in the parabasal layer of normal cervical epithelium and only in the nonkeratinized areas of the cancer nests of invasive keratinizing carcinoma. Most cells in cancer nests of an invasive nonkeratinizing carcinoma were found to be DNA polymerase alpha-positive. In cases of mild or moderate dysplasia DNA polymerase alpha-positive cells were found only in the lower half of the epithelium. DNA polymerase alpha-positive cells in severe dysplasia to carcinoma in situ were distributed throughout the full thickness of the epithelium. The percentages of DNA polymerase alpha-positive cells in mild or moderate dysplasia, severe dysplasia to carcinoma in situ, and invasive carcinoma were 32.2%, 45.7%, and 53.7%, respectively. The authors previously developed immunohistochemical methods for detecting DNA polymerase alpha by monoclonal antibody that allowed the proliferative activity of cells in normal and neoplastic tissues to be estimated.
...
PMID:Detection of proliferative cells in dysplasia, carcinoma in situ, and invasive carcinoma of the uterine cervix by monoclonal antibody against DNA polymerase alpha. 334 75

tsFT20 cells derived from a mouse mammary carcinoma cell line, FM3A, which has temperature-sensitive DNA polymerase alpha activity (Y. Murakami, H. Yasuda, H. Miyazawa, F. Hanaoka, and M. Yamada, Proc. Natl. Acad. Sci. USA, 82:1761-1765, 1985) were rapidly committed to death after temperature upshift to 39 degrees C. tsFT20 cells synchronized in S phase were more sensitive to the restrictive temperature than exponentially growing cells. In order to gain insight into the processes from the interruption of DNA synthesis to cell death, we analyzed chromosome aberrations induced in tsFT20 cells which had been incubated for 2 or 4 h at the restrictive temperature and then cultured at the permissive temperature. The majority of metaphase cells showed extensive chromosome aberrations such as chromatid gaps, breaks, and exchanges; chromosome pulverizations; their mixed types; and ring chromosomes. Analyses with the use of cell synchronization and autoradiography revealed that chromosome aberrations were induced only in the cells which synthesized DNA during incubation at 39 degrees C. We classified the chromosome aberrations into five types: gap or break type; exchange type; pulverization type; complex type; and ring type. The temporal order of the appearance of these types of chromosome aberrations was found to be the above described order. It was further found that cycloheximide dramatically repressed the induction of chromosome aberrations, and metaphases with many chromosome aberrations exhibited a large number of sister chromatid exchanges. These results indicate that abnormal cessation of DNA replication in tsFT20 cells at the restrictive temperature due to the inactivation of DNA polymerase alpha results in cell death via induction of double-strand breaks which lead to chromosome aberrations as well as sister chromatid exchanges.
...
PMID:Characterization of chromosome aberrations induced by incubation at a restrictive temperature in the mouse temperature-sensitive mutant tsFT20 strain containing heat-labile DNA polymerase alpha. 362 Dec 1

tsFT20 cells derived from a mouse mammary carcinoma cell line FM3A have temperature-sensitive DNA polymerase alpha activity (Murakami, Y., Yasuda, H., Miyazawa, H., Hanaoka, F., and Yamada, M. (1985) Proc. Natl. Acad. Sci. U. S. A. 82, 1761-1765). DNA replication in tsFT20 cells at the restrictive temperature (39 degrees C) has been characterized in detail. DNA-synthesizing ability of these cells was measured by [3H] thymidine incorporation and autoradiography. The incorporation of [3H]thymidine decreased rapidly after temperature shift-up, and the incorporation was less than 20% of the initial level after 4 h at 39 degrees C. The rapid decrease correlated well with the decrease in the grain number in the individual nucleus but not with the number of cells with labeled nuclei. Alkaline sucrose gradient sedimentation analysis and DNA fiber autoradiography revealed that DNA chain elongation proceeded normally within a replicon in the temperature-sensitive cells incubated at the restrictive temperature and the DNA elongation rate did not change during the incubation at the restrictive temperature up to at least 6 h. On the other hand, the maturation of replicon-sized DNA to higher molecular weight DNA was retarded or inhibited in the temperature-sensitive cells at the restrictive temperature. The analysis of the center to center distance between replicons by DNA fiber autoradiography revealed that the frequency of replicon initiation decreased in tsFT20 cells at 39 degrees C.
...
PMID:Characterization of DNA replication at a restrictive temperature in a mouse DNA temperature-sensitive mutant, tsFT20 strain, containing heat-labile DNA polymerase alpha activity. 372 80

Virions isolated from a spontaneous mammary carcinoma of a rhesus monkey and propagated in human cells possess an RNA-instructed DNA polymerase. They also exhibit DNA polymerase activities that respond to either double-stranded DNA or synthetic RNA.DNA hybrid complexes as templates. The virion has been shown to have a density of 1.16 g/ml and to contain a nucleic acid species of high molecular weight (sedimentation coefficient, 60-70 S), which bands as RNA at 1.670 in a Cs(2)SO(4) equilibrium density gradient. In addition, the virions contain species of low molecular weight (4-6 S) that consist of RNA as well as components banding at densities characteristic of DNA.RNA complexes. The nucleoid of this virion has been isolated and shown to have a density of 1.23 g/ml; it also contains a 60-70S nucleic acid species.
...
PMID:DNA polymerase activities and nucleic acid components of virions isolated from a spontaneous mammary carcinoma from a rhesus monkey. 528 52

We have demonstrated previously that core structures of urine samples from patients with genitourinary malignancies contain ribonucleic acid-directed deoxyribonucleic acid polymerase and a high molecular weight ribonucleic acid. If these particles originated from the existing genitourinary malignancies then the malignancies should contain similar characteristics. We examined 13 prostatic carcinomas, 4 bladder carcinomas, 1 urethral carcinoma and 1 hypernephroma. Positive reactions were noted in 10 of the 13 prostatic carcinomas (77 per cent), all 4 bladder carcinomas, the 1 urethral carcinoma and the hypernephroma with the simultaneous detection assay. The control samples consisted of 7 tissues of benign prostatic hypertrophy, and tissue from 2 normal bladders and 1 normal kidney. None of these tissues showed a positive response. Tritium labeled deoxyribonucleic acid probes synthesized from the malignant tissues hybridized to the polysomal ribonucleic acids but not to the corresponding normal tissues. Particles derived from the probes have a density of 1,1620 in sucrose gradient. No sequence homology could be demonstrated with various known oncogenic ribonucleic acid viruses nor with malignancies arising from other organs.
...
PMID:Molecular evidence of viral-like biochemical activities in human genitourinary malignancies. 615 80


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---