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)

Full-length radiolabeled albumin and alpha-fetoprotein (AFP) cDNAs were synthesized from pure albumin and AMP mRNA preparations by using avian myeloblastosis virus reverse transcriptase (RNA-dependent DNA polymerase). The cDNAs have been used to quantitate the number of albumin and AFP genes in different rat tissues by two independent methods, both of which yielded similar results. First, the kinetics of the association of these cDNAs with nuclear DNA from rat liver, rat kidney, and Morris hepatoma 7777 under conditions of vast DNA excess indicated that the albumin and AFP mRNA's are transcribed from "nonrepetitive DNA." Second, saturation hybridization experiments in which a constant amount of rat liver DNA or Morris hepatoma 7777 was hybridized with increasing amounts of cDNA to albumin mRNA have shown the presence of 1--2 albumin genes per rat haploid genome. The number of AFP genes obtained in similar titration experiments was approximately 2--3. This was true whether rat liver DNA or hepatoma 7777 DNA was used in the reassociation experiments. When high molecular weight DNA preparations from both these tissues were digested with the restriction endonuclease EcoRI and the fragments were transferred to a nitrocellulose filter, the albumin and AFP [32P]cDNA probes hybridized to different sets of DNA fragments. However, each probe gave the same hybridization pattern whether Buffalo rat liver DNA or hepatoma 7777 DNA was utilized.
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PMID:alpha-Fetoprotein and albumin genes of rats: no evidence for amplification-deletion or rearrangement in rat liver carcinogenesis. 8 3

Estrogen administration to male Xenopus causes the cytoplasmic destabilization of the hepatic serum protein coding mRNAs, most notably, albumin, yet has little effect on mRNAs encoding intracellular proteins such as ferritin. This report describes an estrogen-inducible ribonuclease activity found in liver polysomes that degrades albumin mRNA 4 times faster in vitro than it degrades ferritin mRNA. This differential rate of degradation was observed upon incubation of polysome extract with free liver RNA, isolated liver mRNPs, or transcripts from plasmid vectors. A cleavage fragment consisting of a doublet of approximately 194 nucleotides in length was consistently observed upon digestion of transcripts for the full length or 5' half of albumin mRNA. The generation of this cleavage fragment was used as an assay to study properties of the polysome nuclease activity. The 194 doublet is produced by the action of a Mg(2+)-independent endonuclease. This distinguishes the Xenopus liver enzyme from the enzymes that degrade histone or c-myc mRNA in vitro. It is inactivated by 400 mM NaCl or heating at 90 degrees C, but not by placental ribonuclease inhibitor or N-ethylmaleimide. Finally, the polysomal nuclease activity does not degrade double-stranded RNA. We believe the estrogen-induced nuclease activity contains an enzyme(s) that may mediate hormone-regulated changes in mRNA stability in this tissue.
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PMID:Estrogen-induced ribonuclease activity in Xenopus liver. 193 72

Analysis of AFP and albumin genes fails to demonstrate a correlation of gene activity with the degree of gene methylation as determined by restriction endonuclease fragments obtained using the isoschizomer pair, Hpa II and Msp I. There is no difference in the methylation patterns of DNA from high and low producing tissues, such as fetal and adult liver for AFP, hepatoma 7777 and 9098 for AFP; adult lung, brain, kidney and liver for albumin; fetal liver and brain or heart for AFP, etc. Minor selective differences in gene methylation that correlate with AFP or albumin gene expression cannot be ruled out.
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PMID:Lack of correlation of methylation and alphafetoprotein and albumin gene expression during liver growth, in hepatocellular carcinomas, and during hepatocarcinogenesis. 241 16

We examined the methylation pattern and organization of the AFP gene in whole livers and in isolated cell populations purified from livers of rats fed a carcinogenic diet which interferes with DNA methylation. Using restriction endonuclease digestion, we find no differences in methylation pattern and overall organization of the AFP gene in oval cells (AFP-producers) and hepatocytes (non-producers) isolated at the early stages of carcinogenesis. Our studies indicate that in cell populations which produce AFP as well as in cells which are not active in AFP synthesis, the majority of the CCGG sites of the AFP gene are extensively methylated. In addition, we describe the existence of polymorphism in the AFP and albumin genes of Sprague-Dawley rats.
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PMID:Methylation of the alphafetoprotein gene in cell populations isolated from rat livers during carcinogenesis. 241 27

Functional and structural approaches were used to characterize the transcription units of the rat alpha-feto-protein (AFP) and albumin genes. A cell-free nuclear transcription assay and several genomic clones were used to show that: 1) the rate of transcription of these genes is closely related to the levels of corresponding mRNAs in the yolk sac and during rat liver development, indicating that the expression of the albumin and AFP genes is mainly regulated at the transcriptional level in the rat, and 2) the in vivo 5' end boundaries of the rat AFP and albumin transcription domains were mapped near the respective first exons. Due to the presence of repeated sequences, the 3' end boundary of both genes could not be accurately defined in the same manner. 3) No transcription could be detected until 7 kilobases upstream from the cap site of these genes. In addition, the organization of the rat AFP gene was analyzed by restriction endonuclease mapping, S1 nuclease mapping, and nucleotide sequencing. Our results indicate that: 1) the rat AFP gene is 20 kilobase pairs long and is split into 15 exons by 14 intervening sequences; 2) the transcription initiation site of the rat AFP gene is heterogenous; 3) the 5'-flanking region upstream from the rat AFP gene exhibits 60-90% similarity with the mouse and human AFP genes while no major nucleotide identity is found with the rat albumin gene; 4) a 90-base pair sequence present as one copy upstream from the rat and mouse AFP genes is present as two copies in the human genome; 5) several inverted repeats are mapped in the 5'-flanking region indicating potential stem-loop structures. One highly conserved structure encompasses an enhancer-like core sequence and the sequence recognized by the TGGCA-binding protein.
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PMID:The rat alpha-fetoprotein and albumin genes. Transcriptional control and comparison of the sequence organization and promoter region. 244 63

Previous studies from this laboratory have demonstrated that cytosolic Ca2+ rapidly rises to supraphysiologic levels in liver cells exposed to the hepatotoxins carbon tetrachloride (CCl4) and 1,1-dichloroethylene (DCE) in vivo and in vitro. The present study examines whether this increase in intracellular Ca2+ activates endonucleases that could initiate or contribute to the ensuing hepatotoxic events. Initial experiments demonstrated that there was no generalized breakdown of hepatic DNA in intact rats exposed to CCl4 and DCE, as assessed by the appearance of nucleosomal fragments in liver nuclear DNA separated on agarose gels. Nor was generalized fragmentation observed in DNA isolated from primary hepatocyte cultures exposed to halocarbons, except at very late times following loss of plasma membrane integrity. Endonuclease activation was further examined at a more sensitive level by specifically monitoring hypersensitive sites (HSS) in serum albumin gene. Actively transcribed genes, such as albumin in liver tissue, are extremely sensitive to attack by exogenous nucleolytic enzymes at discrete sites. We speculated that subtle halocarbon-induced endonuclease activation would first become evident at these sites. To locate HSS, DNA was digested with restriction enzymes Eco R1 or Hind III, electrophoresed on agarose gels, blotted onto nitrocellulose, and hybridized to a 32P-labeled 1400 bp rat albumin genomic clone. No cleavage at hypersensitive sites was detected in DNA isolated from rat liver or hepatocyte DNA at early times when elevations of Ca2+ were developing. Thus, these data indicate that endonuclease activation by intracellular Ca2+ and resultant nucleolytic destruction of DNA is not an early event in the hepatotoxicity produced by halocarbons.
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PMID:Halocarbon hepatotoxicity is not initiated by Ca2+-stimulated endonuclease activation. 253 8

The structure of the human corticosteroid binding globulin (CBG) gene has been determined, and restriction endonuclease maps of human placental DNA and cloned genomic DNA indicate that CBG is encoded by a single gene. The transcription unit for hepatic CBG mRNA comprises five exons distributed over approximately 19 kilobases (kb), and nuclease protection and primer extension studies using human liver RNA demonstrate that the first exon spans 70 base pairs (bp). Typical of many eukaryotic promoters, sequences that resemble TATA and CAAT-box motifs are centered 28 bp and 73 bp upstream from the origin of transcription, respectively. In addition, six highly conserved sequence elements, responsible for efficient, liver-specific expression of the mouse albumin gene, are located within the first 200 bp of the 5'-flanking region. Further analysis of a region (500 bp) immediately 5' of the transcription start site, however, failed to reveal sequences that might correspond to known steroid hormone response elements. When compared to other serine protease inhibitor genes, the organization of the human CBG gene is most closely related to the human alpha 1-proteinase inhibitor and alpha 1-antichymotrypsin genes. It would therefore appear that these proteins are derived from a common ancestral gene, and this supports the concept that they may be functionally related.
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PMID:Organization of the human corticosteroid binding globulin gene and analysis of its 5'-flanking region. 260 68

Restriction endonuclease digestion using Hind III and Msp I and Southern blot analysis of DNA from the liver of three inbred rat strains and one outbred strain using cDNA probes yields two banding patterns for the alphafetoprotein and albumin genes. Buffalo and Fischer DNA have one pattern whereas ACI had a different pattern for both genes. Sprague Dawley DNA contains fragments of both patterns suggesting heterozygosity in some individuals of this strain. These polymorphisms do not appear to be associated with any structural or biological differences in the proteins resulting from expression of these genes.
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PMID:Polymorphism of rat alphafetoprotein and albumin genes. 608 1

The murine alpha-fetoprotein (AFP) and albumin genes have been cloned from genomic libraries derived from Balb/c DNA. By restriction endonuclease mapping and electron microscopy, we have shown that both genes are organized similarly into 15 coding segments interrupted by 14 intervening sequences. The sizes of the corresponding coding segments in each gene are identical, lending support to the hypothesis that the two genes, were derived from a common ancestral gene. However, no nucleotide homology between coding segments was observed. Both the sizes and the nucleotide sequence of flanking and intervening sequences have diverged significantly as well. Two regions of the AFP gene, 925 base pairs in the 5' flanking DNA and 180 base pairs in the third intervening sequence, hybridized to the same region of DNA in the third intervening sequence of albumin. The 180-base pair homologies within each gene are present in opposite orientation relative to the direction of transcription, and are associated with reiterated DNA. Thus, it is unlikely that they represent true sequence conservation. An examination of the sizes of the coding segments in each gene reveals a thrice repeated domain, consisting of 4 coding segments. We propose that these correspond to the three domains observed in several mammalian albumins, and in murine AFP.
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PMID:The evolution of alpha-fetoprotein and albumin. II. The structures of the alpha-fetoprotein and albumin genes in the mouse. 616 30

The urine alpha-fetoprotein (AFP) and serum albumin genes most probably arose in evolution as the consequence of a duplication of a common ancestral gene. They have both been previously mapped to chromosome 5 in the mouse. We now have evidence that these genes are closely linked. By using a unique copy DNA probe derived from previously cloned AFP 5' flanking DNA, a recombinant DNA phage has been isolated, from a bacteriophage DNA library, that contains sequences flanking the 5' end of the AFP gene and the 3' end of the albumin gene. Restriction endonuclease mapping and DNA sequence determination of the recombinant phage and comparison to total genomic DNA confirmed that the genes are in tandem, 13.5 kilobase pairs apart, with the albumin gene to the 5' side of the AFP gene. Thus, they are transcribed from the same strand of DNA.
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PMID:alpha-Fetoprotein and albumin genes are in tandem in the mouse genome. 617 Sep 78


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