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)

Lymphocytes from a common human leukemia, chronic lymphocytic leukemia, chronic lymphocytic leukemia, have a greatly enhanced capability of DNA repair and a concomitantly prolonged survival in vitro after damage to DNA. From these lymphocytes, we isolated and purified a DNA-binding protein with a molecular weight of 24,000. It binds tightly to both ultraviolet light (UV)-irradiated and single-stranded DNA. At 35 degrees it enhances the helix-coil transition of poly[d(A-T)] AND the UV-irradiated calf thymus DNA but is inefficient in ordinary native DNA. This protein also facilitates the rate of UV-endonuclease incision of UV DNA but does not induce any nicks by itself. This finding suggests that the protein may be involved in DNA repair by enhancing such activity, and also offers an explanation for our observation of increased DNA repair in chronic lymphocytic leukemia cells. When human metaphase chromosomes are exposed to the protein, it induces marked lengthening of chromatids suggesting that this protein may also act on complex chromosomes. By quantitative immunochemical determinations, such protein could not be found in lymphocyte extracts of three normal individuals.
Cancer Res 1975 Apr
PMID:Some properties of a DNA-unwinding protein unique to lymphocytes from chronic lymphocytic leukemia. 111 55

The recently isolated neutral deoxyribonuclease from crab (Cancer pagurus) testes has been characterized in its mode of action and its specificity. The enzyme is a typical endonuclease, forming 5'-phosphate oligonucleotides of large average size; after extensive digestion of calf thymus DNA over 75% of the fragments have a size larger than pentanucleotides and mononucleotides are absent. As far as specificity is concerned, thymidine is very abundant in the 5'-penultimate position (approximately 50%) and in the 3'-terminal position (37%) and almost absent in the 5'-terminal position (approximately 1%), the values quoted concerning Escherichia coli digests of average size (Pn) between 50 and 10.
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PMID:The specificity of a neutral deoxyribonuclease from Cancer pagurus. 123 41

Androgen-dependent normal prostatic glandular cells and androgen-dependent prostatic cancer cells can be induced to undergo cell death after androgen ablation. This death does not require the cells to proliferate and occurs as an energy-dependent process collectively referred to as "programmed cell death" in which the cells actively commit "suicide." Associated with this programmed cell death pathway is the enhanced expression of a series of genes and the fragmentation of the genomic DNA into nucleosomal oligomers. This genomic DNA fragmentation is the irreversible commitment step in the death of the cell and results from activation of Ca2+/Mg(2+)-dependent endonuclease activity within the cell nucleus. This activation is due to sustained elevation of intracellular free Ca2+ (Cai) induced after androgen ablation. Metastatic prostatic cancer within an individual patient is heterogeneous, including both androgen-dependent and -independent cancer cells. Thus, androgen ablation is rarely curative since it only induces the programmed death of the androgen-dependent cancer cells without activating this pathway in the androgen-independent cancer cells within the patient. Androgen-independent prostatic cancer cells do not activate this death process after androgen ablation, since this does not induce a sustained increase in Cai. A new approach to treat androgen-independent prostatic cancer cells has focused on the use of chemotherapeutic agents to induce a sustained increase in Cai. These studies demonstrate that if such a sustained elevation in Cai is maintained, even androgen-independent prostatic cancer cells undergo programmed cell death.
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PMID:Androgen regulation of programmed death of normal and malignant prostatic cells. 129 27

The doxorubicin-selected multidrug resistant small cell lung cancer cell line, H69AR, is cross-resistant to the Vinca alkaloids and epipodophyllotoxins, but does not overexpress P-glycoprotein, a 170 kDa plasma membrane efflux pump usually associated with this type of resistance. Monoclonal antibodies were raised against the H69AR cell line and one of these, MAb 3.186, recognises a peptide epitope on a 36 kDa phosphorylated protein that is membrane associated, but not presented on the external surface of H69AR cells (Mirski & Cole, 1991). In the present study, in vitro translation and molecular cloning techniques were used to determine the relative levels of mRNA corresponding to the 3.186 antigen. In addition, a cDNA clone containing an insert of approximately 1.4 kb was obtained by screening an H69AR cDNA library with 125I-MAb 3.186. Fragments of this cloned DNA hybridised to a single mRNA species of approximately 1.6 kb that was 5 to 6-fold elevated in H69AR cells. Partial DNA sequencing and restriction endonuclease mapping revealed identity of the cloned DNA with p36, a member of the annexin/lipocortin family of Ca2+ and phospholipid binding proteins.
Br J Cancer 1992 Apr
PMID:Elevated expression of annexin II (lipocortin II, p36) in a multidrug resistant small cell lung cancer cell line. 131 68

DNA breaks can arise from many sources after incubation of cells with toxic agents. Very few agents break DNA directly, rather most breaks occur as a result of metabolic participation by the cell, such as during attempts to repair the damage. It is now realized that many DNA breaks arise as a consequence of steps in the pathway of cell death. Upon reanalyzing the methodology commonly used to detect DNA breaks, it is evident that many studies would not have observed DNA breaks associated with cell death. Frequently experimental conditions have been used that are extremely toxic to cells with the justification that the cells were still viable as measured by their ability to exclude dyes such as trypan blue. However, the DNA digestion associated with cell death by apoptosis occurs prior to changes in membrane integrity. Because the possibility of endogenous endonuclease activity was not realized, many studies may have inaccurately assumed that DNA breaks arose during, for example, inhibition of DNA repair or as intermediates in recombination. In light of the new understanding of apoptosis and the formation of DNA breaks as an early event in cell death, it is important to both reevaluate past conclusions and to ensure that future studies fully consider the breaks derived from the cytotoxicity of every agent under investigation.
Cancer Invest 1992
PMID:The origins of DNA breaks: a consequence of DNA damage, DNA repair, or apoptosis? 131 2

Normal rat fibroblasts exhibit a staged response to anoxia which in several respects parallels processes activated in malignant tumor cells. We describe here a new element of the anoxic response, the induction by anoxia of a sequestered endonuclease activity. Such activity is elevated approximately 3-fold within anoxic fibroblasts and during Hirt DNA isolation is able to digest chromatin to produce a nucleosomal ladder. However, DNA is not measurably affected within intact cells, and cells retain complete viability as the endonuclease is induced. The anoxia-inducible endonuclease acts without specificity for DNA sequence. Trace leakage of this endonuclease into the nucleus has obvious potential to underlie the known propensity of anoxic cells to undergo amplification and may be associated with the break-related genomic instability of cancer cells.
Cancer Res 1992 Aug 15
PMID:Anoxia-inducible endonuclease activity as a potential basis of the genomic instability of cancer cells. 132 86

Apoptosis, or programmed cell death, is an endogenous cellular process whereby an external signal activates a metabolic pathway that results in cell death. This form of cell death appears to be a common feature in many biological processes where cell deletion is a mechanism for altering tissue structure and function. Historically, apoptosis has been studied using histological techniques; however, more recent interest has focused on analyzing this process at the biochemical level. A biochemical hallmark of apoptosis is a characteristic form of DNA degradation in which the genome is cleaved at internucleosomal sites, generating a 'ladder' of DNA fragments when analyzed by agarose gel electrophoresis. A number of assay systems have been developed to study this nuclease activity. For example, nuclease activity has been analyzed by measuring the release of endogenous DNA from apoptotic cells, by flow cytometric analysis of apoptotic cells and by analyzing in situ apoptotic nuclease activity in polyacrylamide gels containing DNA. Use of these assay systems has enabled investigators to study the signal transduction pathways that mediate apoptosis and to characterize the endonuclease itself. Future biochemical studies in this field will focus on isolating the genes and gene products that mediate apoptosis.
Cancer Metastasis Rev 1992 Sep
PMID:A biochemical hallmark of apoptosis: internucleosomal degradation of the genome. 132 65

Differential accessibility to DNA in tumor cell chromatin is important to growth, differentiation apoptosis, and the targeting of DNA modifying drugs. We now show that endonuclease accessibility to DNA in the nuclei of A431 human carcinoma cells is increased within 90 min by nontoxic nanomolar levels of okadaic acid, known to inhibit protein phosphatase 2A. This genomic hypersensitivity was partly enhanced by joint treatment with epidermal growth factor and okadaic acid but did not appear without the latter. Nuclei with greater DNA susceptibility showed a decrease in M(r) 80,000 DNA binding protein doublet specific for dAT-rich sequences concurrent with the "apparent" hyperphosphorylation of a M(r) 70,000 nuclear matrix protein. We propose that some of the tumor-promoting effects of okadaic acid may be partly associated with its ability to promote genomic susceptibility.
Cancer Res 1992 Nov 15
PMID:Accessibility to DNA in carcinoma chromatin is promoted by nanomolar okadaic acid: effect on AT-rich DNA binding proteins. 133 Feb 92

The presence of estrogen receptor (ER) is a well-known predictor of clinical outcome in human breast cancer. We examined the ER gene in 26 primary breast cancers (14 ER-positive, 12 ER-negative) to determine if alterations of the gene are associated with the ER-negative status. In tumor biopsies and peripheral blood DNA obtained from the same patients we analyzed the ER exon structure using polymerase chain reaction amplification, restriction endonuclease digestion, and agarose gel electrophoresis. All blood and tumor samples, regardless of ER status, showed a complete set of eight exons of normal sizes, ruling out deletions or rearrangements of the ER gene in excess of +/- 20 nucleotides. Previous reports indicate that the two-allele ER PvuII polymorphism could be associated with ER expression in breast cancer (Hill et al., Cancer Res., 49: 145-148, 1989) as well as with patient age at time of tumor diagnosis (Parl et al., Breast Cancer Res. Treat., 14: 57-64, 1989). We localized the PvuII polymorphism in intron 1, 0.4 kilobase upstream of exon 2. Sequence analysis showed the polymorphism to result from a point mutation (T----C) at the fifth position of the restriction site (CATCTG). We determined the PvuII restriction fragment-length polymorphism genotype in 257 primary breast cancers and 140 peripheral blood DNA samples obtained from women without breast cancer. The results indicate that the PvuII polymorphism is not associated with ER content or patient age at tumor diagnosis.
Cancer Res 1992 Jan 01
PMID:Analysis of the PvuII restriction fragment-length polymorphism and exon structure of the estrogen receptor gene in breast cancer and peripheral blood. 134 63

DNA amplification, RNA overexpression and p185 protein expression of the c-erbB2 oncogene were investigated in 109 cases of breast cancer with the aim of evaluating any correlation between the different methods. A correlation between Southern blotting and immunohistochemical analysis of paraffin-embedded material was found. Thus, amplification of the c-erbB2 oncogene leads to overexpression of the p185 protein. By contrast, no statistical correlation could be shown between RNA overexpression, measured by Northern blotting, and immunohistochemical p185 membrane stainings. It is of special interest that most of the cases that are positive for Northern blotting and negative for immunochemistry are negative for Southern blotting as well. Contradictory findings between RNA overexpression and lack of immunohistochemical staining of p185 give rise to the assumption that a defective protein is encoded, which cannot be incorporated into the substructures of the tumour cell membrane. When screening for point mutations in the transmembrane domain of the c-erbB2 oncogene, no point mutation could be detected, either by using the endonuclease FokI, which cuts at position 2012 (the point mutation in the neu gene of the rat), or by direct sequencing.
J Cancer Res Clin Oncol 1992
PMID:Alterations of the c-erbB2 gene in human breast cancer. 135 98


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