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)

An integrated view of the processes which most likely play a critical role in the aging process at the cellular level is proposed. Cells are continuously exposed to a variety of internal and external stressors, potentially dangerous for the maintenance of the functional integrity of the cell (UV and gamma radiation, heat, oxygen free radicals, glucose, bacteria, viruses). In the course of evolution a number of mechanisms [DNA repair, production of heat shock and other stress proteins, enzymatic and non-enzymatic antioxidant defence systems, poly(ADP-ribose) polymerase activation] have emerged which allow the cell to cope with such a variety of potentially harmful agents. These mechanisms are in fact interconnected and constitute a network of cellular defence systems. It is suggested that they play a physiological role, being involved in the control of gene expression. A failure of these mechanisms does not allow the cell to maintain homeostasis and has profound consequences as far as two of the major programs of the cell are concerned, i.e. cell proliferation and cell death. Recent data suggesting that these are two physiologically active phenomena tightly linked and regulated are examined. Thus, activation of cell cycle related genes and active inhibition of suicide genes appear to be a part of an integrated process. Conversely, deprivation of growth factors seems able to induce an active process of programmed cell death characterized by Ca++,Mg+(+)-dependent endonuclease activity and DNA fragmentation (apoptosis). Similar phenomena have been shown to accompany the terminal differentiation process in several cellular systems. The understanding of the factors which favour or prevent cell death (a phenomenon which has been recognized as one of the most important in fetal development and morphogenesis) will help to unravel and eventually to manipulate the aging process. In an evolutionary perspective, cell senescence appears to be the price paid to avoid unlimited capability of proliferation, i.e. cell transformation and cancer.
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PMID:Cell proliferation, cell death and aging. 248 97

A primary perianal squamous cell carcinoma and two metastatic tumors from a renal transplant recipient with a previous history of condyloma acuminatum were analyzed by filter hybridization for the presence of human papillomavirus (HPV) DNA. Each of the DNA extracts from these three tissues was found to contain HPV DNA. Stringent hybridization and restriction endonuclease analysis identified this viral DNA as HPV 11 related, which largely comigrated with cellular DNA, suggesting the presence of integrated viral DNA. Each DNA extract was analyzed by two-dimensional gel electrophoresis, which separates circular and linear forms of DNA and can demonstrate linear viral DNA, which comigrated with high molecular weight linear cellular DNA, thus implying viral integration. In all three cases the vast majority of viral DNA was found to comigrate with linear DNA; in addition, a significant portion comigrated with high molecular weight cellular DNA, suggesting the presence of integrated viral DNA in these tumors. Restriction endonuclease analysis of high molecular weight cellular DNA from each of these tumors revealed identical banding patterns, indicating that the integration site in each tissue is identical and, therefore, that all three tumors most likely originated from a single clonal event. These molecular results are presented in light of the clinical history of this patient with a histologically "low grade," but biologically aggressive, squamous cell carcinoma and suggest that HPV 11 may be associated with the initiation of malignant epithelial neoplasms.
Cancer Res 1989 May 01
PMID:Characterization of integrated human papillomavirus type 11 DNA in primary and metastatic tumors from a renal transplant recipient. 253 6

Under certain circumstances sequence-specific inhibition of gene expression may be achieved in intact cells using exogenous anti-sense oligodeoxynucleotides. The efficacy of this approach to investigating gene function is limited in part by the rapid serum nuclease mediated degradation of oligodeoxynucleotides in culture media. In order to determine the relative contributions of 3'-exonuclease, 5'-exonuclease and endonuclease activity in fetal calf serum to oligodeoxynucleotide destruction, we have tested chimeric N-ras anti-sense sequence molecules protected against exonuclease attack with terminal methylphosphonate diester linkages. An 18-mer with two methylphosphonate diester linkages at the 3'-terminus, a 20-mer with two methylphosphonate diester groups at both ends, and the 16-mer 3'-methylphosphonate monoester components of their respective piperidine hydrolysates were totally resistant to venom phosphodiesterase, whereas the 16-mer 3'-hydroxyl components of the hydrolysates were rapidly degraded. Both the chimeric oligodeoxynucleotides and 3'-methylphosphonate monoesters were considerably more stable than normal 3'-hydroxyl oligodeoxynucleotides at 37 degrees C in McCoy's 5A medium containing 15% heat inactivated fetal calf serum. Typically 20-30% of the former (initial concentration 10-100 microM) remained intact at 20 h as compared to the latter which were 88-100% degraded in 4 h and undetectable at 20 h. We conclude that a 3'-phosphodiesterase activity is a predominant nuclease responsible for oligodeoxynucleotide degradation by fetal calf serum, and that for cell culture studies, significant protection of oligodeoxynucleotides may be achieved by incorporating 3'-terminal methylphosphonate diester or even monoester end groups.
Br J Cancer 1989 Sep
PMID:Partial protection of oncogene, anti-sense oligodeoxynucleotides against serum nuclease degradation using terminal methylphosphonate groups. 255 58

The development of human cancer is generally thought to entail a series of events that cause a progressively more malignant phenotype. Such a hypothesis predicts that tumor cells of the ultimate stage will carry each of the events, cells of the penultimate stage will carry each of the events less the last one, and so on. That is to say a dissection of the pathway from a normal cell to a fully malignant tumor may be viewed as the unraveling of a nested set of aberrations. In experiments designed to elucidate these events, we have compared genotypic combinations at genomic loci defined by restriction endonuclease recognition site variation in normal and tumor tissues from patients with various forms and stages of cancer. The first step, inherited predisposition, is best described for retinoblastoma in which a recessive mutation of a locus residing in the 13q14 region of the genome is unmasked by aberrant, but specific, mitotic chromosomal segregation. A similar mechanism involving the distal short arm of chromosome 17 is apparent in astrocytic tumors and the event is shared by cells in each malignancy stage. This is distinct from a loss of heterozygosity for loci on chromosome 10 which is restricted to the ultimate stage, glioblastoma multiforme. These results suggest a genetic approach to defining degrees of tumor progression and means for determining the genomic locations of genes involved in the pathway as a prelude to their molecular isolation and characterization.
Cancer Detect Prev 1989
PMID:Mitotic abnormalities leading to cancer predisposition and progression. 255

C-erbB-2 and epidermal growth factor receptor (EGFR) genes were independently shown to be associated with breast cancer progression. In this report, we have analyzed the structure and expression of these 2 genes in the same tumor specimens of a large series of breast cancers. Two clinical types of tumor were studied: inflammatory (IBC) and non-inflammatory breast cancers (NBC) obtained from 221 untreated patients at different clinical stages. Amplification and over-expression of the c-erbB-2 proto-oncogene were observed in 27% and 47% of tumors, respectively, and were strongly associated with breast cancers of the most unfavorable prognosis, namely IBC and NBC with multiple positive axillary nodes. EGFR gene was neither amplified nor rearranged. A restriction fragment length polymorphism (RFLP) for HindIII endonuclease was observed. EGFR transcripts were detected in 46% of tumors and observed more frequently in IBC than in NBC (p less than 0.02). In NBC the presence of EGFR transcripts increased linearly with lymph-node involvement and was associated with estrogen-receptor-negative tumors (p = 0.01). Analysis of both genes from the same tumor samples indicated that genes are associated with cancer aggressiveness. Furthermore, in NBC these 2 genes were independently activated, in contrast to IBC in which activated genes were negatively correlated, suggesting that c-erbB-2 and EGFR genes play different roles in NBC and IBC.
Int J Cancer 1989 Feb 15
PMID:Structure and expression of c-erbB-2 and EGF receptor genes in inflammatory and non-inflammatory breast cancer: prognostic significance. 256 19

Chromosome 5 allele loss is a genetic alteration occurring during the multistep progression of colon carcinogenesis. To determine whether a similar genetic alteration occurs in other gastrointestinal malignancies, the authors have analyzed DNA extracted from freshly frozen normal and neoplastic tissue from nineteen patients who underwent radical resections for gastric, ampullary and pancreatic adenocarcinomas at the University of Chicago. Loss of heterozygosity for alleles on the long arm of chromosome 5 was detected in tumor DNA compared to normal tissue DNA from the same patient using restriction fragment length polymorphisms (RFLPs). Eleven patients were informative using the restriction endonuclease TaqI to generate RFLPs for chromosome 5 probes C11 P11 and pTP5E. Loss of heterozygosity was found in one of eight informative gastric carcinomas (12.5%) and in one of two informative ampullary carcinomas. The only informative pancreatic adenocarcinoma was heterozygous. It is concluded that chromosome 5 allele loss occurs in a variety of gastrointestinal malignancies and suggest that common genetic origins may underlie these different tumors.
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PMID:Chromosome 5 allele loss in human gastric, ampullary and pancreatic carcinomas. 257 24

The methylation state of DNA from human colon tissue displaying neoplastic growth was determined by means of restriction endonuclease analysis. When compared to DNA from adjacent normal tissue, DNA from both benign colon polyps and malignant carcinomas was substantially hypomethylated. With the use of probes for growth hormone, gamma-globin, alpha-chorionic gonadotropin, and gamma-crystallin, methylation changes were detected in all 23 neoplastic growths examined. Benign polyps were hypomethylated to a degree similar to that in malignant tissue. These results indicate that hypomethylation is a consistent biochemical characteristic of human colonic tumors and is an alteration in the DNA that precedes malignancy.
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PMID:Hypomethylation of DNA from benign and malignant human colon neoplasms. 257 35

The methylation patterns of the gag, pol, env, pX and LTR regions of proviral DNA of human T-cell leukemia/lymphoma virus type I (HTLV) in fresh leukemic cells and established cell lines were examined using HpaII/MspI endonuclease. Peripheral blood lymphocytes (PBL) isolated from patients with adult T-cell leukemia/lymphoma (ATL) did not express viral antigens of HTLV, but PBL that had been cultured for 2 days did express these viral antigens. Most parts of the gag, pol and env regions of the HTLV provirus in PBL isolated from 12 ATL patients and PBL cultured for 2 days were hypermethylated as reported by others. In contrast, in 10 established cell lines that harbored HTLV genomes and expressed viral antigens, HTLV proviruses were hypomethylated. In one cell line, ATL-IK, which harbored an HTLV genome but did not produce viral antigens, the gag, pol and env regions were hypermethylated. However, two HpaII sites, one in the middle of the gag region and the other in the middle of the pol region, were not methylated even in PBL from most ATL patients. Furthermore, the pX and LTR regions were hypomethylated not only in established cell lines but also in PBL of ATL patients. The hypomethylation of the pX and LTR regions detected in fresh leukemic cells of ATL patients may have some etiological significance in cell transformation by controlling the level of transcription of these regions, or modulating the binding of some factors to these regions.
Int J Cancer 1985 May 15
PMID:Methylation pattern of human T-cell leukemia virus in vivo and in vitro: pX and LTR regions are hypomethylated in vivo. 258 3

Southern blot analysis of 6 human bladder carcinoma cell lines revealed amplification of the epidermal growth factor receptor (EGFR) gene in the KU1 cell line. The amplification of the gene was about 4-fold as compared with that of human placental DNA. Several restriction endonuclease digestions revealed that there was no gross rearrangement of the EGFR gene in KU1. Northern blot analysis showed normal 10 and 5.6 kb of EGFR gene-related mRNA species. 125I-EGF binding revealed 2 distinct EGF binding sites on KU1 cells: high-affinity sites 5.7 X 10(5) receptors per cell with 1.1 nM Kd and low-affinity sites 2.3 X 10(6) receptors per cell with 7.4 nM Kd. The number of the EGFR was compatible with that of the A431 squamous carcinoma cell ine which has an amplified, rearranged and over-expressed EGFR gene. Solid-phase immuno-isolation analysis showed a single 170 kDa EGFR protein in KU1 as well as in A431. Unlike other cell lines with amplified and over-expressed EGFR gene, anchorage-dependent growth of KU1 was stimulated but not inhibited by EGF. Moreover, anchorage-independent growth of KU1 was stimulated by EGF.
Int J Cancer 1989 Dec 15
PMID:EGF stimulates anchorage-independent growth of a human bladder carcinoma cell line (KU1) with an amplified and over-expressed EGF receptor gene. 260 69

Covalently closed circular DNA containing a synthetic analog of an abasic site at a unique position was used as a substrate to study DNA repair. Incubation of this DNA in Xenopus laevis oocyte extracts resulted in rapid cleavage of the DNA at the abasic site by a class II apurinic-apyrimidinic endonuclease, followed by complete repair within 40 min. Nicked circular DNAs persisted for several minutes before repair by an ATP-dependent DNA synthesis reaction. The repair-related DNA synthesis was localized within 3 or 4 nucleotides surrounding the abasic site. These results are consistent with the short-patch repair reported for DNA damage at heterogeneous sites in human cells (J. D. Regan and R. B. Setlow, Cancer Res. 34:3318-3325, 1974).
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PMID:Repair of a synthetic abasic site in DNA in a Xenopus laevis oocyte extract. 277 65


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