Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of dimethylnitrosamine on functional activities of liver chromatin was studied in mice. After a single dose of dimethylnitrosamine injected i.v. (25 mg/kg body wt, 45 min before sacrifice) liver nuclei were isolated and incubated with micrococcal nuclease (EC 3.1.4.7) to an acid-solubility of 2.5% of total DNA. Chromatin was fractionated into a 1,200 g pellet P1, 102,000 g pellet P2 and supernatant fraction S2. Chromatin-bound RNA polymerase I plus III activity decreased 15% in the P1 and 25% in the P2 fraction. No changes in activity were observed in the S2 fraction. Chromatin-bound RNA polymerase II activity decreased 19% in the P1, 49% in the P2 and 32% in the S2 fraction. Heparin stimulated RNA polymerase II activity decreased 10% in the P1 and 44% in the P2 fraction. Formation of initiation in nuclear lysates with RNA polymerase from Escherichia coli increased after administration of dimethylnitrosamine suggesting an increase in the number of sites available for the start of new RNA chains. The results show that limited digestion of nuclei with endonuclease cleaves chromatin regions which are more affected by dimethylnitrosamine than the total chromatin suggesting a non-random effect of the hepatotoxin on chromatin. Modifications of the DNA template by dimethylnitrosamine is indicated by the change in number of initiation complexes.
 ...
PMID:Non-random effect on RNA synthesis in liver chromatin by administration of dimethylnitrosamine to mice. 619 51

Extracts of HeLa cells containing RNA polymerase II and other factors recognize specific sites on linear simian virus 40 (SV40) DNA for initiation of transcription. The most prominent RNA products transcribed from the early region of SV40 and th E strand are initiated at sites 0.67 and 0.655 on the SV40 map. These two RNAs are synthesized by polymerase II. Their 5' termini were positioned by sizing transcripts that extend from the initiation site to the end of the template restriction endonuclease fragment, and by S1-nuclease mapping of unlabeled RNA using DNA probes labeled at their 5' termini. The limit of resolution of mapping of 5' termini is approximately 25 nucleotides. RNAs with 5' termini at similar positions have been found during characterization of mRNAs produced in infected cells. Thus, the whole cell extract is probably initiating transcription on linear SV40 DNA in vitro at the same sites as RNAs synthesized in vivo. Two other processes frequently involved in mammalian cell mRNA biosynthesis, creation of specific 3'-terminal polyadenine tracts and RNA splicing, were not detected during the course of these studies.
 ...
PMID:Transcription of Simian virus 40 DNA in a HeLa whole cell extract. 625 54

mRNA's homologous to the herpes simplex virus type 1 DNA restriction endonuclease fragment BamHI p, which contains the thymidine kinase gene, have been identified and mapped by hybrid-arrested translation and mRNA selection. Such mRNA's, when translated in vitro, directed the synthesis of polypeptides of apparent molecular weights 43,000 (VI43) and 39,000 (VI39). mRNA for enzymatically active thymidine kinase was enriched by more than 20-fold after selection. Mapping was carried out with restriction endonuclease fragments of BamHI p, and locations of the 5' and 3' termini of VI43 mRNA were deduced. Analysis of nucleotide sequences around the 5' terminus revealed several consensus sequences commonly found at the start of eucaryotic mRNA's and which are presumably involved in initiation of transcription by RNA polymerase II. Translation of mRNA's for VI43, VI39, and the thymidine kinase enzyme was arrested only by a 1,170-base-pair region of BamHI p. Since this region is insufficient for adjacent genes, coding sequences for VI43 and VI39 must overlap; the possible relationship of these two polypeptides is discussed. A virus-induced product equivalent to VI39 was detected in infected cells.
 ...
PMID:Identification and mapping of two polypeptides encoded within the herpes simplex virus type 1 thymidine kinase gene sequences. 626 30

Nascent RNA, synthesized by calf thymus ENA polymerase II on the restriction endonuclease EcoRI fragment A and BamHI fragment B of adenovirus 2 DNA, was rehybridized to the template strand under conditions allowing transcription R-loop formation. Hybrids, visualized by electron microscopy, were found in looped and in branched configurations, the former being abundant, with an average loop number of roughly four per EcoRI fragment A and three per BamHI fragment B. Frequency distributions of transcription R-loops, synthesized on identical restriction fragments for different periods of time, showed similar patterns, thus pointing to a nonrandom type of transcription. A comparison of the frequency distribution of R-loops seen on the two overlapping restriction fragments reveals reasonable coincidence in the loop pattern in one out of the four possible fragment orientations, permitting correlation of the transcription R-loop pattern with the physical map of the adenovirus 2 DNA. Comparison of start sites tentatively mapped in vitro with the known promoters for RNA polymerase II in vivo suggests that a major transcription site in vitro is located in close proximity to, or identical with, two promoters in vivo at 16.1 and 16.5 map units.
 ...
PMID:R-loop mapping of calf-thymus RNA polymerase II. Transcripts in vitro on restriction fragments of adenovirus 2 DNA. 627 22

We describe a 2560 base pair herpes simplex virus type 1 (HSV-1) DNA sequence containing the entire immediate-early mRNA-5 (IEmRNA-5) gene. The 3' and 5' termini of IEmRNA-5 were mapped within this DNA sequence by single-strand specific endonuclease protection experiments. The IEmRNA-5 gene contains DNA sequences from both the unique (Us) and reiterated (TRs/IRs) regions of the HSV-1 DNA short component and is interrupted by a single intron mapping in TRs/IRs. A search of the transcribed DNA sequence revealed no initiator codon within TRs/IRs. The first ATG was located 6 bases into Us sequences and this reading frame (316 codons) was also observed in the 3' transcribed region. The oligonucleotide sequences adjacent to the IEmRNA-5 termini are discussed in relation to those of the HSV-1 thymidine kinase gene and other genes transcribed by RNA polymerase II.
 ...
PMID:DNA sequence of an immediate-early gene (IEmRNA-5) of herpes simplex virus type I. 627 43

We employed an in vitro cell-free transcription system to locate RNA polymerase II promoters on the hepatitis B virus genome. The strongest promoter precedes the surface antigen (HBsAg) gene, which is comprised of a long (500 base pairs) presurface region as well as the mature HBsAg coding sequence. The origin of this transcript was localized by using truncated templates and S1 endonuclease mapping. The activity of the promoter was confirmed in transfection experiments in which the complete HBsAg gene was introduced into monkey kidney cells via a simian virus 40 expression vector. A second RNA polymerase II promoter preceding the HBcAg gene was also active in the cell-free system. The presence of multiple promoters in the hepatitis B virus genome suggests that the relative levels of viral-specific proteins detected in liver and serum may reflect differential or regulated promoter efficiency.
 ...
PMID:Transcription of hepatitis B virus by RNA polymerase II. 664 22

Synthesis of influenza virus mRNA is primed by capped and methylated (cap 1, m7GpppXm) RNAs which the virus derives by endonucleolytic cleavage from RNA polymerase II transcripts in host cells. The conserved nature of the endonucleolytic processing provides a unique target for the development of antiviral agents for influenza viruses. A series of 4-substituted 2,4-dioxobutanoic acid compounds has been identified as selective inhibitors of this activity in both influenza A and B viruses. These inhibitors exhibited 50% inhibitory concentrations in the range of 0.2 to 29.0 microM for cap-dependent influenza virus transcription and had no effect on the activity of other viral and cellular polymerases when tested at 100- to 500-fold higher concentrations. The compounds did not inhibit the initiation or elongation of influenza virus mRNA synthesis but specifically inhibited the cleavage of capped RNAs by the influenza virus endonuclease and were not inhibitory to the activities of other nucleases. Additionally, the compounds specifically inhibited replication of influenza A and B viruses in cell culture with potencies comparable to the 50% inhibitory concentrations obtained for transcription.
 ...
PMID:Inhibition of cap (m7GpppXm)-dependent endonuclease of influenza virus by 4-substituted 2,4-dioxobutanoic acid compounds. 769 69

Nucleotide excision repair (NER) in eukaryotes is a biochemically complex process involving multiple gene products. The budding yeast Saccharomyces cerevisiae is an informative model for this process. Multiple genes and in some cases gene products that are indispensable for NER have been isolated from this organism. Homologues of many of these yeast genes are structurally and functionally conserved in higher organisms, including humans. The yeast Rad1/Rad10 heterodimeric protein complex is an endonuclease that is believed to participate in damage-specific incision of DNA during NER. This endonuclease is also required for specialized types of recombination. The products of the RAD3, SSL2(RAD25) SSL1 and TFB1 genes have dual roles in NER and in RNA polymerase II-dependent basal transcription.
 ...
PMID:Nucleotide excision repair in the yeast Saccharomyces cerevisiae: its relationship to specialized mitotic recombination and RNA polymerase II basal transcription. 774 56

A 26-kDa endonuclease has been purified to homogeneity from zinc-sufficient Euglena gracilis. The protein binds to single-stranded DNA with a higher affinity than to double-stranded DNA, but it exhibits nucleolytic activity toward both. Thus, it converts supercoiled plasmid pBR322 DNA into the linear form, a property characteristic of endonucleases, and it continues to act on the linearized DNA until it is completely degraded. It also hydrolyzes heat-denatured, single-stranded calf thymus DNA. Moreover, at amounts below 1 microgram, it enhances RNA synthesis by RNA polymerase II, a characteristic observed with other DNases. Its addition to an in vitro transcription assay increases RNA synthesis up to 3-fold. The nuclease requires two metal components to carry out its enzymatic activities. It hydrolyzes DNA only in the presence of millimolar amounts of magnesium or micromolar quantities of other activating metal ions, such as manganese, zinc, or cobalt. However, even when optimal concentrations of Mg2+ are present, micromolar amounts of the metal-chelating agents OP and HQSA completely inhibit pBR322 digestion. Transcription enhancement is also inhibited completely by both chelators at concentrations that do not affect the intrinsic polymerase II activity. By atomic absorption spectrometry, the enzyme contains 1 g-atom of Zn/mol, which is the likely target of chelator action. The nuclease protein can also be isolated from zinc-deficient E. gracilis, but remarkably it then contains 1 mol of Cu/g-atom and no zinc.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:A Euglena gracilis zinc endonuclease. 844 31

Influenza virus, a negative strand RNA virus, cannibalizes host cell, capped RNA polymerase II transcripts in the nucleus via a process termed "cap-snatching". The viral transcriptase enzyme; which is composed of a complex of the three viral polymerase (P) proteins, contains a cap-dependent endonuclease that cleaves capped cellular RNAs in the nucleus 10-13 nucleotides from their 5' ends. The resulting capped RNA fragments are required as primers for the initiation of viral mRNA synthesis. In the 18 year since the discovery of "cap-snatching" it has not been determined how the viral transcriptase exhibits selectivity and "snatches" caps from cellular, but not viral, mRNAs. Here we elucidate the surprising mechanism of this selectivity: the complex of the same three viral P proteins that catalyzes "cap-snatching" is also responsible for selectivity protecting the 5' ends of viral, but not cellular, mRNAs from "cap-snatching". The viral P protein complex is able to acquire these two very different functions because this complex lacks any detectable activity unless it binds to one or more specific RNA sequences. Here we demonstrate that the viral P protein complex binds to the common sequence in all the viral mRNAs that is immediately 3' to the 5' sequence that is "snatched" from host cell RNAs. This binding activates the cap-binding activity of the P protein complex, thereby enhancing its binding to the capped viral mRNA. We show that these P protein complexes protect the 5' ends of viral mRNAs from endonucleolytic cleavage by the viral transcriptase, whereas the 5' ends of nonviral mRNAs are not protected.
 ...
PMID:Surprising function of the three influenza viral polymerase proteins: selective protection of viral mRNAs against the cap-snatching reaction catalyzed by the same polymerase proteins. 895 65


<< Previous 1 2 3 4 5 6 7 Next >>