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

The production of mouse mammary tumor virus (MMTV) in primary cell cultures of BALB/cfC3H mammary tumor cells was measured by radioimmune assay and RNA=dependent DNA polymerase activity. Maximum virus production was dependent on cell density, nutritional milieu, and hormone supplementation. The addition of insulin (u), estradiol-17 beta (E2), progesterone (P), prolactin (PRL), or thyroxine (T3) alone had little or no effect on MMTV production. Hydrocortisone (F) had a primary stimulatory effect. The combination of I, F, and T3 increased MMTV levels. The combinations containing I, F, and E2 had the greatest stimulatory effect. The stimulation of MMTV production was dose dependent. These experiments demonstrate that a variety of hormones act in a synergistic manner to stimulate MMTV production.
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PMID:Hormone synergism in the in vitro production of the mouse mammary tumor virus. 18 27

Host-range variants of mouse mammary tumor virus (MMTV) have been isolated that have the ability to productively infect cells in vitro with high efficiency (at multiplicities of infection </=1) and with extremely short latent periods to the production of de novo virus (as short as 4 days after infection). These variants of the highly oncogenic MMTV of RIII, C3H, and GR mice were obtained by serial virus passage in feline cells. The resultant variant stocks react in group-specific radioimmunoassays for the MMTV major external glycoprotein (gp52) and major internal protein (p28), possess a protein profile similar to that of wild-type MMTV, and contain a virion-associated DNA polymerase with a magnesium cation preference. Addition of dexamethasone and insulin to culture media enhances the titer of de novo MMTV to levels of approximately 10(10) particles per 75-cm(2) flask (containing 5 x 10(6) cells) per 24 hr. Variant stocks exhibit no evidence of contamination with either murine or feline type C retroviruses, as assayed by various techniques. The variants of MMTV derived from C3H and RIII mice exhibit differential host ranges that include the ability to productively infect feline, canine, bat, mink, murine, and human cells. Use of these MMTV host-range variants now facilitates the study of the complete replicative cycle of MMTV as well as an elucidation of the interaction of MMTV with various hormones, physical or chemical carcinogens, and tumor promoters in the initiation and promotion of mammary neoplasia.
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PMID:Isolation of host-range variants of mouse mammary tumor viruses that efficiently infect cells in vitro. 21 96

Human mammary carcinoma cell cultures proliferated from primary explants in Eagle's essential medium (MEM) supplemented with insulin, fetal calf serum (FCS) and/or human alpha-a1-antitrypsin. Human mammary carcinoma cells differed from normal mammary epithelial cells by the following catalytic activities: a. Thymidine uptake into the carcinoma cells was 6 to 10 fold greater, whereas thymidine conversion to CO2 was half to one fifth that of normal cells. b. The nucleolytic activity patterns of the mammary carcinoma cells preferred polycytydylic acid and double helical polynucleotides, whereas those of the normal mammary cells preferred polyuridylic acid and had no effect on double helical polynucleotides. c. The polymerase activity most evident in mammary carcinoma cells is a hybrid-dependent DNA polymerase which is guided by the ribo-strand of the template poly (rA) . poly(dT). In contrast the all-ribo template poly (rA) . poly(rU) showed little activity. d. There was slight or statistically non-significant difference between the amino acid composition of material cleaved from mammary carcinoma cells prepared from tumor tissues and from cells cultivated 10 months in vitro. e. There was no difference between the molar proportions of the carbohydrate components of the cell membrane from fresh tumor tissue and long term in vitro cultivated cells. f. The granules from long term in vitro cultured mammary carcinoma cells contained high collagenolytic, caseinolytic, fibrinolytic and esterolytic activities.
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PMID:Long-term cultivation of human mammary carcionoma: proliferation and differential biochemical properties of the cultured cells. 51 50

The entire 2nd thoracic mammary gland of the immature virgin BALB/c mouse was stimulated to full lobulo-alveolar (LA) growth after 120 h organ culture in hormone supplemented medium. The minimal hormonal combination required was insulin (I) + prolactin (Prl) + aldosterone (A). The corticosteroid was replaceable by oestradiol-17beta (E) + progesterone (P). The combination I alone or I + the steroid hormone(s) failed to induce the LA development and similar results were also evident in presence of Prl + the steroids. Incubation of the glands in medium with I + Prl + A activated a sequential rise of RNA, protein and DNA synthesis. A near maximal increase of RNA synthesis was present at 48 h in the medium with I + Prl, addition of the steroid hormones did not show further stimulatory effect. Supplementation of the medium with I + Prl and the adrenal or the ovarian steroids was needed for maximal activation of protein synthesis at 72 h and DNA replication at 96 h. The medium with I alone did not show a substantial rise of macromolecular biosynthesis in the mammary gland in organ culture. The highest level of DNA polymerase activity was observed at 72 h in glands cultivated in medium with I + Prl and A or E + P. Only a modest increase of DNA polymerase activity was present in glands cultivated with I alone or I + Prl. Prior treatment of the glands (cultivated with I + Prl + A) with actinomycin D or puromycin resulted into 44 and 40% reduction of DNA polymerase activity suggesting hormone-induced synthesis of the enzyme before the rise of DNA synthesis in the mammary cells at 96 h in organ culture. Significance of these results with respect to the action of the "growth-promoting" hormones in the mammary gland in organ culture and in the animal has been discussed.
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PMID:Action of growth-promoting hormones on macromolecular biosynthesis during lobulo-alveolar development of the entire mammary gland in organ culture. 124 65

A study was made of the repair of ionizing radiation-induced DNA single-strand breaks (SSB) in proliferating and quiescent mouse Swiss 3T6 cells and in those stimulated from the quiet status by epidermal growth factor in combination with insulin, in the presence of specific inhibitors of DNA polymerase alpha and delta (aphidicolin) and DNA polymerase beta (2', 3'-dideoxythymidine-5'-triphosphate). The repair of DNA SSB induced by X-ray-irradiation (10 Gr) or by gamma-ray irradiation (150 Gr) is more sensitive to aphidicolin independently of cell proliferating status. Aphidicolin inhibits the recovery of single-strand DNA in quiescent and mitogen-stimulated cells three times stronger than in proliferating cells. The influence of 2', 3'-dideoxythymidine-5'-triphosphate on the rate of DNA SSB repair in cells of all the three types does not differ. Thus, the decrease in DNA repair efficiency in quiescent cells is connected with a decrease in the activity of aphidicolin-sensitive DNA polymerase, apparently DNA polymerase alpha. It is suggested that the regulation action of mitogens on the DNA SSB repair may be determined by qualitative changes of this enzyme or of some conditions in which it functions. The involvement of DNA polymerase delta in this process is not excluded.
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PMID:[The regulation of the DNA repair process in mammalian cells. IV. The role of DNA polymerases in the epidermal growth factor regulation of the repair of single-stranded DNA breaks induced by ionizing radiation in Swiss 3T6 mouse cells]. 129 56

The autocrine, paracrine, or systemic growth factors responsible for fetal lung cell growth are not completely defined. The progression-type insulin-like growth factors and epidermal growth factor, or transforming growth factor-alpha acting through the epidermal growth factor receptor, appear to act on the developing lung epithelium. The competence factors that facilitate the actions of progression factors during lung growth are unknown. Fetal rat lung cells in vitro synthesize a platelet-derived growth factor (PDGF)-like polypeptide, which we have hypothesized may play a paracrine role in normal lung development. Slot blot and Northern blot analyses of fetal rat lung mRNA have been used to determine if there is a relationship between expression of message for PDGF-A or PDGF-B chains, or their cognate receptors, and periods of maximal growth during late fetal rat lung development. Whole lung mRNA was extracted on 18, 19, 20, 21, and 22 days of gestation (term = 22 days). The peak of DNA synthesis, as assessed by expression of message for DNA polymerase alpha, histone 3, and the proto-oncogenes c-fos and c-myc, which are stimulated by binding of growth factors including PDGF, occurred during the canalicular stage of lung development on days 19 and 20 of gestation. Expression of message for PDGF-A and PDGF-B chains was low during the pseudoglandular stage on day 18, peaked during the canalicular stage on days 19 and 20, then fell again during the saccular stage at days 21 and 22 of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Platelet-derived growth factor and growth-related genes in rat lung. I. Developmental expression. 191 Aug 22

All prokaryotic and eukaryotic thioredoxins contain a conserved tryptophan residue, exposed at the active site disulfide/dithiol. The role of this W31 in Escherichia coli thioredoxin (Trx) was studied by site-directed mutagenesis. Four mutant Trx with W31Y, W31F, W31H, and W31A replacements were characterized. Very low tryptophan fluorescence emission from the remaining W28 was observed in all mutant Trx; reduction resulted in large, but variable increases (up to 11-fold) of fluorescence, to levels higher than in native or denatured wild-type Trx, demonstrating a previously postulated change involving W28. All W31 mutant Trx were good substrates for E. coli thioredoxin reductase. Compared with wild type, the apparent Km values were increased less than 2-fold for the W31A, W31H, and W31F Trx and the W31Y Trx showed even slightly higher catalytic efficiency (kcat/Km value). Functions of reduced Trx with ribonucleotide reductase and in reduction of insulin disulfides were more strongly influenced by the W31 replacements, in particular at low pH for A and H residues. T7 DNA polymerase activity generated by T7 gene 5 protein and reduced Trx was lowered by large factors for W31Y, W31A, or W31H compared with W31F or the wild-type protein. The in vivo function of Trx was studied by using pUC118-trxA expression in an E. coli trxA- background. The trxA genes with W31Y and W31F substitutions restored, fully and partly, the methionine sulfoxide utilization of a trxA- metE- test strain; W31A and W31H mutations resulted in no growth. Propagation of M13 was moderately impeded by W31Y and W31F or severely by W31A and W31H replacements. Growth of a phage T3/7 hybrid was possible only with the W31Y and W31F substitutions reflecting the in vitro results for T7 DNA polymerase.
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PMID:Substitution of the conserved tryptophan 31 in Escherichia coli thioredoxin by site-directed mutagenesis and structure-function analysis. 199 1

In Chinese hamster embryo fibroblast cells, an increase in intracellular calmodulin levels coincided with the nuclear localization of a calmodulin-binding protein of about 68 kDa as the cells progressed from G1 to S phase. When cells were limited from entering into S phase, by omitting insulin a defined medium, intracellular CaM levels did not increase and the 68 kDa calmodulin-binding protein was completely absent from the nuclei. Corresponding to the nuclear localization of calmodulin and the 68 kDa calmodulin-binding protein in S phase cells, there was a dramatic increase in DNA polymerase and thymidine kinase activities in the nuclei of S phase cells as compared to G1 phase cells. In addition, the 68 kDa calmodulin-binding protein, along with calmodulin, is observed to be an integral component of replitase complex responsible for nuclear DNA replication in S phase cells. These observations point to the association of calmodulin and calmodulin-binding protein(s) with the replication machinery responsible for nuclear DNA replication during S phase. A possible regulatory role of these proteins in the onset of DNA replication and cell proliferation is discussed.
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PMID:Nuclear localization of 68 kDa calmodulin-binding protein is associated with the onset of DNA replication. 220 42

Mutations in the insulin receptor gene can render the cell resistant to the biological action of insulin. We have studied a patient with leprechaunism (leprechaun/Minn-1), a genetic syndrome associated with intrauterine growth retardation and extreme insulin resistance. Genomic DNA from the patient was amplified by the polymerase chain reaction catalyzed by Thermus aquaticus (Taq) DNA polymerase, and the amplified DNA was directly sequenced. A nonsense mutation was identified at codon 897 in exon 14 in the paternal allele of the patient's insulin receptor gene. Levels of insulin receptor mRNA are decreased to less than 10% of normal in Epstein-Barr virus-transformed lymphoblasts and cultured skin fibroblasts from this patient. Thus, this nonsense mutation appears to cause a decrease in the levels of insulin receptor mRNA. In addition, we have obtained indirect evidence that the patient's maternal allele of the insulin receptor gene contains a cis-acting dominant mutation that also decreases the level of mRNA, but by a different mechanism. The nucleotide sequence of the entire protein-coding domain and the sequences of the intron-exon boundaries for all 22 exons of the maternal allele were normal. Presumably, the mutation in the maternal allele maps elsewhere in the insulin receptor gene. Thus, we conclude that the patient is a compound heterozygote for two cis-acting dominant mutations in the insulin receptor gene: (i) a nonsense mutation in the paternal allele that reduces the level of insulin receptor mRNA and (ii) an as yet unidentified mutation in the maternal allele that either decreases the rate of transcription or decreases the stability of the mRNA.
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PMID:A nonsense mutation causing decreased levels of insulin receptor mRNA: detection by a simplified technique for direct sequencing of genomic DNA amplified by the polymerase chain reaction. 230 May 53

Insulin resistance is an early predictor of development of noninsulin-dependent diabetes mellitus (NIDDM) in Pima Indians, a population with the highest reported prevalence of NIDDM. The insulin receptor plays a central role in mediating insulin action, and previous studies have demonstrated that mutations in the insulin receptor gene may cause insulin resistance. Therefore, we have cloned the insulin receptor cDNA from an insulin-resistant Pima Indian to determine if there is a mutation in the patient's insulin receptor gene. We obtained nine cDNA clones spanning exons 4-10 and 12-22 of the patient's insulin receptor gene. Polymorphisms in the nucleotide sequences for codons 523 (Ala), 1058 (His), and 1062 (Leu) provided useful markers to differentiate the patient's two alleles of the insulin receptor gene. These substitutions were silent, in that they did not alter the predicted amino acid sequence. The sequence of exons 1-3 and 11 was determined directly from genomic DNA that had been amplified using the polymerase chain reaction catalyzed by Taq DNA polymerase. Other investigators have reported defects in insulin binding and insulin receptor tyrosine kinase activity in diabetic Pima Indians. However, we did not detect any mutations in this patient's insulin receptor gene. Thus, these observations are consistent with the interpretation that the defects in insulin receptor function are acquired rather than derived from defects in the primary structure of the receptor.
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PMID:The amino acid sequence of the insulin receptor is normal in an insulin-resistant Pima Indian. 231 37


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