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)

Allelic deletions of the p53 gene previously were demonstrated by Southern hybridization to occur in high frequency in sporadic colon carcinomas and in a variety of other human tumors. We have examined the frequency of allelic loss of the p53 gene in carcinoma and dysplasia arising in patients with chronic ulcerative colitis who are heterozygous for the codon 72 polymorphism in exon 4 of the p53 gene. Cells derived from carcinoma and dysplasia specimens from 10 patients who were heterozygous at this locus were sorted by flow cytometry on the basis of DNA content. The p53 exon 4 region was amplified from diploid and aneuploid populations, via a polymerase chain reaction (PCR), and digested with BstUI. Three of three carcinomas, four of six dysplasias, and one patient who was indefinite for dysplasia demonstrated evidence of allelic loss of the p53 gene. Seven of ten cases of sporadic colon carcinoma, analyzed for comparative purposes, exhibited loss of a p53 allele. These results demonstrate that PCR analysis, followed by restriction endonuclease digestion of a polymorphic locus, can provide a rapid, definitive method for analyzing loss of heterozygosity in small numbers of cells from colonic mucosa. Such loss precedes cancer in ulcerative colitis and can be present in its earliest histologically identifiable precursor.
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PMID:Frequent loss of a p53 allele in carcinomas and their precursors in ulcerative colitis. 204 25

Genomic DNA and mRNA from the adenocarcinoma cell line LoVo were used to generate L-cell transfectants and a bacteriophage lambda gt11 cDNA clone that express epitopes of carcinoembryonic antigen (CEA). Primary and secondary L-cell transfectants expressing CEA were selected with a fluorescence-activated cell sorter (FACS). These transfectants, including some clones that were selected for high-level CEA expression by multiple rounds of FACS sorting, express a surface protein of 150 kDa that reacts with all anti-CEA antibodies tested. In parallel, a cDNA library of LoVo poly(A)+ RNA was constructed in lambda gt11 and fusion proteins were screened with polyclonal antisera against CEA. One positive clone, lambda cLV7, was identified that hybridized specifically to transfectant DNA. The nucleic acid sequence of the cDNA insert (cLV7) contained two regions of extensive internal homology, with greater than 70% identity at the amino acid level. cLV7 hybridized to three mRNA species of LoVo cells and to a predominant mRNA of the CEA-expressing transfectants. Hybridization of cLV7 to restriction endonuclease-digested genomic DNA of colon carcinoma cells, normal human cells, and human-mouse somatic cell hybrids revealed the presence of multiple hybridizing bands, one of which was present in transfectant cells. These CEA-related sequences are not rearranged in tumors and, by somatic cell hybrid analysis, were mapped to human chromosome 19.
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PMID:Carcinoembryonic antigen family: expression in a mouse L-cell transfectant and characterization of a partial cDNA in bacteriophage lambda gt11. 295 15

We have screened different cultured cell lines established from human tumors for the ability of their DNAs to induce transformed foci in NIH/3T3 cells. Based on restriction endonuclease digestions and the presence of human sequences in mouse transformants, we conclude that five of these human tumor cell lines contain a gene or genes capable of transforming mouse cells and that at least three different transforming genes are present in these five lines. Three cell lines, two derived from lung carcinomas and one derived from a colon carcinoma, transfer the same or closely related human genes. If these transforming genes are mediating the tumorigenic state of the human cells, then our results indicate that overlapping pathways leading to tumorigenesis may arise independently.
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PMID:Human-tumor-derived cell lines contain common and different transforming genes. 610 Dec 1

The ability of extracts of human tumor cells to demethylate O6-methylguanine (O6-MeG) in DNA was assayed using the synthetic DNA polymer poly(dC,dG,m6dG). Cell strains proficient in repair of O6-MeG in vivo (Mer+ phenotype) contained a methyltransferase activity while repair deficient cells (Mer- phenotype) had little or no activity. Mixing extracts of different Mer- strains did not result in the appearance of the activity. Extracts of Mer- cells did not inhibit the activity in extracts of Mer+ cells. Both Mer+ and Mer- strains contained methylnitrosourea-damage-specific endonuclease activity. The data suggest that the Mer- strains are deficient in methyltransferase and that this is the fundamental reason for their hypersensitivity to the cytotoxic effects of DNA alkylation. The activity was partially purified from a Mer+ colon carcinoma cell strain. Its kinetics parallel the repair of O6-MeG in DNA in vivo and suggest that the activity is inactivated during repair of DNA.
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PMID:Repair of O6-methylguanine in DNA by demethylation is lacking in Mer- human tumor cell strains. 682 8

A new sequence-specific RNase was isolated from human colon carcinoma T84 cells. The enzyme was purified to electrophoretical homogeneity by pH precipitation, HiTrapSP and Superdex 200 FPLC. The molecular weight of the new enzyme, which we have named RNase T84, is 19 kDa. RNase T84 is an endonuclease which generates 5'-phosphate-terminated products. The new RNase selectively cleaved the phosphodiester bonds at AU or GU steps at the 3' side of A or G and the 5' side of U. 5'AU3' or 5'GU3' is the minimal sequence required for T84 RNase activity, but the rate of cleavage depends on the sequence and/or structure context. Synthetic ribohomopolymers such as poly(A), poly(G), poly(U) and poly(C) were very poorly hydrolysed by T84 enzyme. In contrast, poly(I) and heteroribopolymers poly(A,U) and poly(A,G,U) were good substrates for the new RNase. The activity towards poly(I) was stronger in two colon carcinoma cell lines than in three other epithelial cell lines. Our results show that RNase T84 is a new sequence-specific enzyme whose gene is abundantly expressed in human colon carcinoma cell lines.
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PMID:New sequence-specific human ribonuclease: purification and properties. 970 18

Cancer development requires the accumulation of numerous genetic changes, which are believed to initiate through the presence of unrepaired lesions in the genome. In the absence of proficient repair, genotoxic agents can lead to crucial mutations of vital cellular genes via replication of damaged DNA. Many cell cycle regulatory proteins are known to modulate the repair capacity and consequently the fate of cells. We and others have recently shown that p53 tumor suppressor gene product is required for efficient global genomic repair (GGR) but not the transcription coupled repair (TCR) of the nucleotide excision repair (NER) sub-pathways. In order to discern the nature of the p53 modulation to be direct or indirect through a downstream mediator, we have investigated the processing of UV radiation induced lesions in human colon carcinoma, HCT116 cells expressing wild-type p53 but having different p21(waf1cip1) (hereafter p21) genotypes (p21+/+, p21+/-, p21-/-). Following 20 J/m(2) UV, all the three cell lines showed rapid increase in p53 protein but the accompanying increase in the expression of its downstream target protein p21 could only be seen in p21+/+ and p21+/- cells and not in p21-/- cells. Nevertheless, an absence of detectable p21 protein in deficient cells had no demonstrable effect on DNA repair response to UV irradiation, as measured by an immunoassay to detect removal of UV photoproducts from genomic DNA (GGR) and by individual strand specific removal of endonuclease-sensitive CPD from a target gene fragment (TCR). Introduction of cytomegalovirus (CMV)-driven luciferase reporter plasmid, UV damaged in vitro, into the un-irradiated cells of varying p21 background, revealed a relatively small but statistically significant decrease in the reporter expression in the host p21-/- as compared with p21+/+ and p21+/- HCT116 cells. Super-expression of p21 protein upon reintroduction of p21 expression construct, showed an enhanced recovery of UV damaged reporter activity that was not greatly different from a similar enhancement observed with undamaged plasmid reporter DNA. Taken together, the results indicate that (i) the p21 protein does not have a significant role in the repair of genomic DNA at chromosomal level; (ii) the well-established p53 dependent modulation of NER is distinct and independent of its cell cycle checkpoint function; and (iii) the reproducible enhancing effect of p21 expression observed through host cell reactivation (HCR) of extrachromosomal DNA is mainly attributable to an effect exerted on transcription rather than repair.
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PMID:Human cells deficient in p53 regulated p21(waf1/cip1) expression exhibit normal nucleotide excision repair of UV-induced DNA damage. 1189 54

Stage II colorectal carcinoma is characterized by negative lymph node pathology as determined by conventional microscopic examination. These patients generally do not receive adjuvant therapy although 20%-30% will die from metastatic disease. To determine whether K-ras mutations at codon 12 could be used as a sensitive indicator of occult lymph node metastasis in stage II colon carcinoma, a retrospective study was performed using restriction endonuclease-mediated selective polymerase chain reaction (REMS-PCR) amplification. Of 106 colonic tumors analyzed, 46 were identified as positive for a K12-ras mutation in the primary tumor. Multiple lymph node samples from 38 of these 46 patients were examined by a sensitive nested PCR protocol for the presence of a K12-ras mutation. Of these 38 patients, 14 had 1 or more positive lymph nodes by PCR (37%) and 24 were negative for the mutation (63%). Of the 14 patients with a K12-ras mutation detected in lymph nodes, 8 died of the disease within 5 years (57%) compared to only 4 of the 24 patients with ras-negative lymph nodes (17%). The difference in time to death from disease, stratified using K12-ras status of lymph nodes, was statistically significant (P = 0.036; log-rank test). These results suggest K-ras mutation status of lymph nodes in patients with stage II colon cancer might identify a subgroup of patients who are more likely to develop recurrent and/or metastatic disease and benefit from adjuvant therapy. Larger studies are indicated to determine whether detection of K-ras mutation positivity in histologically negative lymph nodes portends a poor prognosis and to determine whether more aggressive use of adjuvant therapy is warranted.
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PMID:Detection of mutated K12-ras in histologically negative lymph nodes as an indicator of poor prognosis in stage II colorectal cancer. 1244 69