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)

Rat hepatoma cells infected with mouse mammary tumor virus contain multiple forms of unintegrated viral DNA when grown in the presence of glucocorticoids. Using the DNA transfer procedure of Southern, we have prepared restriction endonuclease fragment maps of these forms of viral DNA. The maps indicate that: (i) the major species of viral DNA is a linear molecule of 5.9 X 10(6) Mr located in the cytoplasm; (ii) the nuclei contain covalently closed circular viral DNA of two distinct sizes (5.1 X 10(6) and 5.9 X 10(6) Mr) in addition to linear molecules (5.9 X 10(6) Mr); (iii) the linear molecule has specific termini; (iv) there is extensive homology between regions at or near termini of the linear molecule; (v) the predominant form of circular DNA lacks 1.2 kilobase pairs present in both the larger circular molecule and the linear molecule; and (vi) the sequences deleted from the majority of the circular DNA molecules are located at the ends of the linear DNA that are joined during circularization.
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PMID:Mapping of linear and circular forms of mouse mammary tumor virus DNA with restriction endonucleases: evidence for a large specific deletion occurring at high frequency during circularization. 20 50

Recently we described a new endogenous proretrovirus of dwarf hamster Phodopus sungorus (MRS-Ps). Its sequence possesses evident homology with the endonuclease domain of the mouse mammary tumor virus pol gene. Here we present nucleotide sequence data on three clones of retroviral long terminal repeats. As many as 15% of substituted, deleted, and inserted base pairs were found while comparing these sequences. Hence, MRS-Ps seems to be rather an old genetic element which originated about 30 million years ago. One LTR is 877 bp long and contains numerous elements that control its transcriptional activity: TATA-box, glucocorticoid responsive element, NF1-binding site, etc. Nevertheless, this LTR does not govern efficient transcription of adjacent genes in a transient expression assay. In addition, we failed to find MRS-specific mRNA in adult, embryonic, and mammary tumor cells.
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PMID:Long terminal repeats of dwarf hamster endogenous retrovirus are highly diverged and do not maintain efficient transcription. 199 85

Sequences in the human genome with homology to the murine mammary tumor virus (MMTV) pol gene were isolated from a human phage library. Ten clones with extensive pol homology were shown to define five separate loci. These loci share common sequences immediately adjacent to the pol-like segments and, in addition, contain a related repeat element which bounds this region. This organization is suggestive of a proviral structure. We estimate that the human genome contains 30 to 40 copies of these pol-related sequences. The pol region of one of the cloned segments (HM16) and the complete MMTV pol gene were sequenced and compared. The nucleotide homology between these pol sequences is 52% and is concentrated in the terminal regions. The MMTV pol gene contains a single long open reading frame encoding 899 amino acids and is demarcated from the partially overlapping putative gag gene by termination codons and a shift in translational reading frame. The pol sequence of HM16 is multiply terminated but does contain open reading frames which encode 370, 105, and 112 amino acid residues in separate reading frames. We deduced a composite pol protein sequence for HM16 by aligning it to the MMTV pol gene and then compared these sequences with other retroviral pol protein sequences. Conserved sequences occur in both the amino and carboxyl regions which lie within the polymerase and endonuclease domains of pol, respectively.
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PMID:Murine mammary tumor virus pol-related sequences in human DNA: characterization and sequence comparison with the complete murine mammary tumor virus pol gene. 241 14

The mechanism of intracellular deoxyribonucleoside-triphosphate (dNTP) imbalance death of mouse mammary tumor FM3A cells was studied. When the cells were exposed to 5-fluorodeoxyuridine, deoxyadenosine, or 2-chlorodeoxyadenosine, dNTP pool imbalance resulted. The imbalance was followed by DNA double-strand breaks and subsequent cell death. The DNA double strand breaks were directly examined by means of orthogonal-field-alternation gel electrophoresis (OFAGE). Fragmented DNA band appeared to be approximately 100-200 kbp in size. The bases of 5'-termini in the DNA were cytosine and thymine. The imbalance induced endonuclease has been isolated by DEAE-agarose column chromatography.
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PMID:dNTP imbalance and DNA double strand breaks in mouse FM3A cells and the mechanism of cell death. 257 44

A highly leukemogenic virus (DMBA-LV) induces thymic lymphomas with a very short (40 days) latent period. All induced tumors contain low numbers of new integrated DMBA-LV type-B proviruses and tumorigenicity of DMBA-LV is completely abolished by a monoclonal antibody directed toward an envelope determinant present on a type-B mammary tumor-inducing viral isolate. While the DMBA-LV type-B genome is very highly related to mammary tumor-inducing isolates it does have unique gp52 and p28 proteins as well as unique restriction endonuclease sites. In the present study the target cell specificity of DMBA-LV was contrasted with that of the mammary tumor-inducing isolate MMTV (C3H). The results indicated that infection of CFW/D mice with DMBA-LV could be detected in the thymus only as early as 17 days postinfection and by 40 days postinfection all 40 thymuses examined contained new integrated proviral copies of DMBA-LV. In contrast, when mice were injected intrathymically with MMTV (C3H) virus infection was transiently detected in the thymus only at 28 days postinfection. By 35 and 42 days postinfection there was no indication that virus-infected cells were still present. Analysis of individual thymic lobes following DMBA-LV infection suggested that independent tumors may be initiated in each of the separate lobes. Furthermore, there appeared to be a correlation between the weight of the lobe and the number of new DMBA-LV proviral copies, the larger the lobe the greater the number of newly integrated proviral copies.
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PMID:Characterization of early molecular biological events associated with thymic lymphoma induction following infection with a thymotropic type-B retrovirus. 282 9

We isolated and characterized a type B thymotropic retrovirus (DMBA-LV) which is highly related to mouse mammary tumor virus (MMTV) isolates and which induces T-cell thymomas with a high incidence and a very short latent period. Regions of nonhomology between the DMBA-LV genome and the MMTV genome were identified by heteroduplex mapping and nucleotide sequence studies. In the electron microscope heteroduplex mapping studies the EcoRI-generated 5' and 3' fragments of the DMBA-LV genome were compared with the corresponding fragments of the MMTV (C3H and GR) genome isolated from mammary tumors. The results indicated that DMBA-LV contained a region of nonhomologous nucleotide sequences in the 3' half of the U3 region of the long terminal repeat (LTR). Nucleotide sequence studies confirmed these results and showed that in this region 440 nucleotides of the MMTV (C3H) sequences were deleted and substituted with a segment of 122 nucleotides. This substituted segment in the form of a tandem repeat structure contained nucleotide sequences derived exclusively from sequences which flanked the substitution loop. The distal glucocorticoid regulatory element was unaltered, and two additional copies of the distal glucocorticoid regulatory element-binding site were present in the substituted region. The restriction endonuclease map of the reconstructed molecular clone of DMBA-LV was identical to that corresponding to unintegrated linear DMBA-LV DNA present in DMBA-LV-induced tumor cell lines. Since the nucleotide sequences of the LTRs present in four different DMBA-LV proviral copies isolated from a single thymoma were identical, we concluded that they were derived from the same parental virus and that this type B retrovirus containing an alteration in the U3 region of its LTR could induce thymic lymphomas. Thus, DMBA-LV represents the first example of a productively replicating type B retrovirus that contains an LTR modified in the U3 region and that has target cell and disease specificity for T cells.
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PMID:Alterations in the U3 region of the long terminal repeat of an infectious thymotropic type B retrovirus. 283 15

We determined the complete nucleotide sequence of the intracisternal A-particle gene, IAP-H18, cloned from the normal Syrian hamster liver DNA. IAP-H18 was 7,951 base pairs in length with two identical long terminal repeats of 376 base pairs at both ends. On the coding strand, imperfect open reading frames corresponding to gag and pol of the retrovirus genome were observed, whereas many stop codons were present in the region corresponding to env. The putative H18 gag gene (809 amino acids) had a sequence homologous to the N-terminal half of the mouse mammary tumor virus gag gene and locally to the Rous sarcoma virus gag gene. The putative H18 pol gene (900 residues) was homologous to the Rous sarcoma virus pol gene almost throughout the entire region. Two conserved regions among the retrovirus pol genes have been reported. One presumably corresponds to the DNA polymerase and the RNase H domain, and the other corresponds to the DNA endonuclease domain of the multifunctional protein pol. By the comparison of the deduced amino acid sequences of the putative endonuclease domain of six representative oncovirus genomes, a phylogenetic tree of the oncovirus genomes was constructed, and the intracisternal A-particle (type A) genome was found to be more closely related to the mouse mammary tumor virus (type B) and squirrel monkey retrovirus (type D) genomes.
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PMID:Nucleotide sequence of the Syrian hamster intracisternal A-particle gene: close evolutionary relationship of type A particle gene to types B and D oncovirus genes. 299 63

Mouse mammary tumor virus (MMTV) is integrated in the genome of most mice as an endogenous provirus. Two of these MMTV proviral loci (Mtv-1 and Mtv-2) are associated with virus expression and tumorigenicity. We prepared restriction endonuclease maps of the endogenous MMTV proviruses in two strains, DBA and GR, which contain the Mtv-1 and Mtv-2 loci, plus a third strain, NFS, which has a low mammary tumor incidence. We find that all these mouse strains have certain MMTV loci in common even though their origins are widely divergent. We also find that some integrated MMTV proviruses appear to have undergone alterations or deletions when compared with MMTV exogenous proviral DNA. We have thus made a comprehensive characterization of MMTV loci in these mouse strains which could serve as a basis for the study of their differences in expression.
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PMID:Restriction endonuclease map of endogenous mouse mammary tumor virus loci in GR, DBA, and NFS mice. 300 33

We sequenced two recombinant DNA clones constituting a single provirus of the milk-transmitted mouse mammary tumor virus characteristic of BR6 mice. The complete provirus is 9,901 base pairs long, flanked by 6 base-pair duplications of cellular DNA at the site of integration. Five extensive blocks of open reading frame corresponding to the gag gene, the presumed protease, the pol and env genes, and the open reading frame orf within the long terminal repeat of the provirus were readily discernible. Translation of gag, protease, and pol involved three different translational reading frames to produce the three overlapping polyprotein precursors Pr77, Pr110, and Pr160 found in virus-infected cells. Synthesis of the reverse transcriptase and endonuclease therefore required two separate frameshifts to suppress the termination codons at the ends of the Pr77 and Pr110 domains. Direct evidence is presented for translational readthrough of both stop codons in an in vitro protein synthesis system.
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PMID:Complete nucleotide sequence of a milk-transmitted mouse mammary tumor virus: two frameshift suppression events are required for translation of gag and pol. 302 77

The 5-methylcytosine content of mouse mammary tumor virus (MMTV)-specific DNA sequences acquired by both milk-borne infection and genetic transmission was determined for both normal and neoplastic tissues of the mouse. Using the restriction endonuclease Msp I, which cleaves at the recognition sequence 5'-CCGG, and its isoschizomer Hpa II, which is inhibited by methylation of the cytosine base of the CpG dinucleotide, it can be demonstrated that MMTV proviruses acquired via germ line infection are extensively methylated at both the site for Msp I-Hpa II cleavage and the site for Hha I (5'-GCGC), which is also inhibited by base modification of the cytosine. The virus-specific sequences acquired via milk-borne infection, however, are not modified at these sites in DNA from either normal infected or transformed tissues. Finally, cellular sequences are nonspecifically hypomethylated in a phenomenon unique to transformed tissue and apparently unrelated to the specific hypomethylation of exogenously acquired MMTV proviruses.
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PMID:Methylation of milk-borne and genetically transmitted mouse mammary tumor virus proviral DNA. 624 94


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