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)

Ten astrocytomas were tested for gene amplification or rearrangement utilizing distinct probes to nine different oncogenes by Southern hybridization. The probes spanned the four major protein-coding classes of oncogenes; growth factor proteins (csis); growth factor receptor/tyrosine kinase-related proteins [erbB1 (epidermal growth factor receptor, EGF-R), neu (HER2/neu, erbB2), mos, yes]; nuclear binding proteins (c-myc, c-fos); and guanosine 5'-triphosphate binding proteins (N-ras, H-ras). Three astrocytomas, all glioblastomas, showed amplification of EGF-R-related sequences, and two of these amplifications were rearranged. Both rearrangements appeared similar by two different restriction endonucleases. Our findings suggest that it is primarily the EGF-R protooncogene (erbB1) that is amplified or rearranged in astrocytic neoplasms. No other oncogenes were amplified or rearranged, although EGF-R and neu cross-hybridization produced a "pseudo-rearranged" pattern for neu in EGF-R-amplified cases. The similar EGF-R restriction endonuclease abnormalities seen in two patients warrant further study.
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PMID:Oncogene abnormalities in astrocytomas: EGF-R gene alone appears to be more frequently amplified and rearranged compared with other protooncogenes. 167 68

Two H-ras oncogenes were detected by NIH/3T3 transfection assay out of 16 primary kidney tumors, 15 renal cell carcinomas (RCC), and one transitional cell carcinoma in 16 patients. Analysis of ras Mr 21,000 protein suggested single point mutations within codon 12 and 61 in each case. The restriction endonuclease analysis of H-ras gene at codon 12 confirmed this in one of them, and the remaining 15 tumors did not have a mutation at this site. DNAs from the noncancerous portions of the kidney with codon 12 mutated tumor, but not leukocytes from the same patient, showed an abnormal resistance to the endonucleases MspI and HpaII, suggesting a presence of codon 12 mutated H-ras gene in the noncancerous cells. No amplification of ras genes was detected in the 16 tumors analyzed. In one of eight tumors from patients heterozygous for H-ras related BamHI restriction fragments, one allele was lost in the tumor but not in the noncancerous portion of the same kidney. Although cytogenetic studies have previously suggested nonrandom involvement of c-raf-1 gene in RCC, no abnormality in the size nor amount of raf transcript was detected in the 15 RCCs. Our results thus indicated that the genetic lesions affecting ras genes do occur in human RCC, and probably serve as one of multisteps in the carcinogenic process.
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PMID:Activated H-ras oncogenes in human kidney tumors. 245 38

We determined a complete nucleotide sequence of an activated form of the c-H-ras-1 proto-oncogene cloned from the human cell line (QG56), using the DNA transfection technique and NIH3T3 cells as recipients. This cell line was established from a squamous-cell lung carcinoma of a Japanese patient, and the activated gene had 2 nucleotide substitutions. One substitution of a thymidine for an adenosine was found at position 1069 of the 2898 nucleotide sequence in a restriction endonuclease (SacI) fragment, which corresponds to the second base of the 61st codon of the gene encoding P21 protein. This nucleotide replacement was assumed to be responsible for the transforming activity. Another substitution of a guanosine for an adenosine which was detected at position 746 in the first intron was thought to be a genetic polymorphism unassociated with the transforming activity. Comparison of the various lengths of restricted fragments suggested that the activity was markedly influenced by certain sequences flanking the c-H-ras-1 gene.
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PMID:Isolation and characterization of an activated C-H-ras-1 gene from a squamous-cell lung carcinoma cell line. 400 2

Cell suicide, or apoptosis, is now recognized as an essential regulatory step in such diverse developmental processes as embryogenesis, thymocyte restriction, and hematopoiesis. One of the major features of apoptosis is the activation of an endogenous nuclease that cleaves DNA into nucleosomal fragments. Little is known about the activation or specificity of the apoptotic endonuclease. In this study, we investigated signalling pathways and the specificity of the apoptotic nuclease. We found that forced over-expression of activated H-ras inhibited activation of the apoptotic endonuclease. Since a high percentage of myelodysplasias and leukemias have mutations that activate ras, this finding lends insight into how ras might be leukemogenic. In addition, the phorbol ester TPA and a cyclic AMP analogue also slowed activation of this endonuclease. Interestingly, protein synthesis inhibition stimulated the endonuclease activity. In addition, by cloning and sequencing apoptotic fragments we found that the apoptotic nuclease has no sequence specificity. Thus, the apoptotic nuclease inhibited by H-ras over-expression was random in nature.
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PMID:Mutant H-ras over-expression inhibits a random apoptotic nuclease in myeloid leukemia cells. 768 29

Excision repair of pyrimidine dimers was examined at the genome overall in three strains of hairless (hr/hr) and congenic wild-type mice, as well as in the expressed H-ras gene in hairless mice. The assay used a pyrimidine dimer-specific endonuclease from Micrococcus luteus and alkaline agarose gel electrophoresis. From 0 to 25% of endonuclease-sensitive sites were removed at the genome level in either hairy or hairless mice but about 50% were removed in the H-ras gene in hairless mice by 24 h after exposure to 5.4 J/cm2 UV (290-400 nm) irradiation. No differences were observed in the repair capacity between hairy and hairless mice, thus eliminating defective DNA repair as the explanation for the greater susceptibility to UV carcinogenesis in hairless mice.
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PMID:Pyrimidine dimer induction and removal in the epidermis of hairless mice: inefficient repair in the genome overall and rapid repair in the H-ras sequence. 801 16

Oncogenes and oncosuppressors can deregulate cell replication in tumours, and recently have been shown to influence the probability of apoptosis. The effects of human c-myc and mutated (T24) Ha-ras oncogenes on susceptibility to apoptosis were investigated by introducing them into immortalised rat fibroblasts. The resulting family of transfectants showed closely similar measures of proliferation, but widely divergent rates of apoptosis, differing by up to fifteen-fold, that correlated inversely with population expansion rates in vitro. T24-ras transfectants with moderate or high p21ras expression showed reduced apoptosis, and this was reversed by pharmacological inhibition of membrane localisation of p21ras by mevinolin. In contrast, c-myc stimulated apoptosis, and this was further enhanced by serum deprivation. Inducibility of effector proteins represents one possible mechanism of genetic control of the susceptibility to apoptosis, and its investigation showed that c-myc was associated with expression by viable cells of latent calcium/magnesium sensitive endonuclease activity characteristic of apoptosis. In contrast, endonuclease activity was not detected in viable cells of a T24-ras transfectant expressing high levels of p21ras. Thus, there appeared to be differential regulation of susceptibility to apoptosis, positively by c-myc and negatively by activated ras, and this was associated with availability of endonuclease activity. Genetic modulation of apoptosis in human neoplasms is likely to influence net growth rate, retention of cells acquiring new mutations and response to certain chemotherapeutic agents.
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PMID:Susceptibility to apoptosis is differentially regulated by c-myc and mutated Ha-ras oncogenes and is associated with endonuclease availability. 826 Mar 64

Most genotoxic DNA base modifications localized at key genomic sequences constitute the molecular alterations crucial or mutagenesis and tumorigenesis. We have utilized lesion-rendered inhibition of restriction endonuclease cleavage for the analysis of site-specific DNA damage induced by (+/-)-7,8-dihydroxy-anti-9, 10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (benzo[a]pyrene diol epoxide, anti-BPDE) in human genes. The H-ras protooncogene and insulin gene sequences were used as targets for modification in vitro and in vivo. Selective induction of individual facultative bands, resulting from covalent modification of the cognate recognition sites, was observed in modified plasmid DNA for a number of restriction nucleases. The ras gene-specific damage, at the PstI, BstYI, NotI and BstEII recognition sites, was visualized and quantitated in human genomic DNA adducted by anti-BPDE. Repair of lesions at hexanucleotide sequences and/or regions surrounding the restriction site, was assessed as a gradual disappearance of facultative bands in DNA from repair-proficient human fibroblasts exposed to the carcinogen in confluent culture. Efficiency of the PstI site-specific repair was compared at low and high levels of initial damage. Higher genotoxic dose caused a decrease in the extent of adduct removal from the bulk DNA, while the specific site of the ras gene was still subject to fast repair. No measurable PstI site-specific repair was detected in the insulin gene. These results show the region-selective induction of bulky anti-BPDE DNA damage in non-related genomic targets and suggest that repair of these lesions in human cells proceeds with the efficiency tightly controlled at different levels of initial genotoxic load.
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PMID:Site-specific induction and repair of benzo[a]pyrene diol epoxide DNA damage in human H-ras protooncogene as revealed by restriction cleavage inhibition. 863 76

Various studies have shown that oncogene and oncosuppressor gene activity can enhance or suppress programmed cell death (apoptosis) in various cell systems. Recent data indicates that overexpression of activated H-ras could influence that onset of apoptosis. We investigated the role of activated H-ras in the apoptotic cell death of rat fibroblast lines. We found that forced overexpression of H-ras induced resistance to U.V. and drug induced apoptosis. We examined possible mechanisms for the action of H-ras in resistance to apoptosis. It was found that both ras transfected and ras untransfected lines displayed similar endonuclease activities. In addition, it was found that the irradiated ras transfected line showed inhibited production of peroxides compared to the irradiated ras untransfected line. Drug induced apoptosis did not appear to involve peroxide production. In addition the antioxidant compound PDTC, was found to inhibit U.V. induced apoptosis but not drug induced apoptosis. In addition, we found the ras transfected line to possess elevated levels of catalase compared to the parent untransfected line. Thus we suggest that an anti-oxidant mechanism, possibly mediated by forced overexpression of activated H-ras could protect cells from apoptosis.
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PMID:Mutant H-ras overexpression inhibits drug and U.V. induced apoptosis. 871 88

The development of atherosclerotic plaques is characterised by the accumulation of lipids and the proliferation of smooth muscle cells. At the subcellular level, the abnormal expression of cytokines and growth factors, as well as the presence of transforming oncogenes, has been recognised and associated with the disease. The aim of the present study was to investigate whether instability at a minisatellite region located downstream of the H-ras proto-oncogene possessing enhancer activity, is a detectable phenomenon in atherosclerotic plaques. Thirty specimens were analysed by polymerase chain reaction (PCR) in order to reveal alterations of the repetition number and by restriction fragment length polymorphism (RFLP) with BstNI restriction endonuclease for the detection of point mutations within the 28 bp core repetitive element. No point mutations were found among the 30 cases tested; however, alterations of the repetition number of the core were detected in 5 (17%) cases. Our results suggest that instability at the H-ras minisatellite may be associated with development of the disease.
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PMID:Instability at the H-ras minisatellite in human atherosclerotic plaques. 883 26

Two molecular-genetic markers-H-ras and YNH24 (chromosome 2)-were tested for genetic linkage with schizophrenia in eight Russian families with different forms of the disease. Thirty-nine subjects, including 13 affected ones, were examined. Five alleles represented as DNA fragments from 2.4 to 4.0 kb in size were detected in DNA samples from probands and other family members when the H-ras probe and TagI restriction endonuclease were used. Eleven alleles were identified in hybridization experiments with YNH24 as a probe. Linkage tests between marker alleles and the schizophrenia predisposition gene were performed by means of the sib-pair method. Statistically significant evidence (5% significance level) for linkage between allele 2 of H-ras and the gene controlling predisposition to schizophrenia was found.
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PMID:[Linkage analysis of schizophrenia with markers of chromosomes 2 and 11 in russian families]. 896 84


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