Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.31.1 (micrococcal nuclease)
 2,818 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bleomycin (BLM) exclusively affects thymidine-containing compounds such as DNA and polydeoxyribonucleotides by releasing free thymine and leaving aldehyde functions. Molecular morphology and base sequence of the DNA strongly influence BLM activity. High BLM concentrations, besides modifying DNA into oligothyminic or athyminic nucleic acids, cause strand scissions. Enzymatic DNA and RNA synthesis is strongly influenced by BLM. The inhibition in DNA-dependent DNA polymerase and DNA-dependent RNA polymerase assays is of the non-competitive type. Protein biosynthesis in in vitro systems is not affected by BLM even at high concentrations. BLM turns out to be a strong inhibitor of DNase I and of DNase II; the inhibition is of the competitive type. The enzymatic activities of nucleases using RNA as substrate (RNase A, RNase B, Rnase T1, venom phosphodiesterase I and spleen phosphodiesterase II) are not influenced by this antibiotic. The antibiotic reduces cell proliferation (L5178y mouse lymphoma cells) in vitro in low concentrations by cytostasis and at higher concentrations by cytotoxicity. In BLM-treated L5178y cells, DNA synthesis is strongly reduced, while RNA and protein synthesis are not affected. In vivo, using growing quail oviducts, cell proliferation and cytodifferentiation are markedly inhibited after BLM treatment. This is attributed to the observed inhibition of DNA synthesis. RNA and protein synthesis as well as gene expression are not influenced by BLM under the conditions used. The selective inhibition of DNA synthesis in vivo may be caused by the following mechanisms: (1) competition of BLM with RNA; (2) blocking of the accessibility of DNA in chromatin to BLM, and (3) dependence from the repair processes. BLM inhibits growth of sarcomas, induced by oncogenic RNA viruses in vivo; well-developed tumours show regression after BLM treatment. Transformation of chick embryo fibroblasts by oncogenic RNA viruses in vitro and growth of these viruses is blocked by BLM; the most sensitive period for BLM inhibition is the time during the first period (integration of viral genome into cellular genome?) after infection.
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PMID:Effect of bleomycin on DNA, RNA, protein, chromatin and on cell transformation by oncogenic RNA viruses. 6 69

Nuclei were isolated from mouse lymphoma L5178Y cells in the exponential growth phase, and chromatin was prepared by mechanical treatment of the nuclei. The nuclei and the chromatin were then digested to various extents with micrococcal nuclease and the resulting mono- and dinucleosome fractions of the two preparations were compared. During progressive digestion mononucleosomes from chromatin retained H1 histone and a DNA length of 165 base pairs, whereas those from nuclei released H1 histone and the length of their DNA decreased to 140 base pairs at an early stage of digestion. These nucleosomal preparations were always associated with nonhistone proteins. The dinucleosomes from nuclei contained larger amounts of nonhistone proteins than those from chromatin, but half of these proteins was released during the process of cleavage into mononucleosomes. The final mononucleosome preparation from nuclei retained 20% less nonhistone proteins than that from chromatin. The contents of nonhistone proteins in mono- and dinucleosomes from chromatin were the same. The electrophoretical distributions of molecular species of nonhistone proteins in mononucleosomes from nuclei and chromatin were different from each other: during digestion the profile of the former changed, whereas that of the latter remained constant. It is tentatively concluded that both H1 histone and nonhistone proteins were bound to nucleosomes more or less loosely in intact nuclei in situ, but that when the nuclear structure was disrupted these proteins became more tightly bound.
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PMID:Artificial structure of chromatin derived in the preparation process. 684 51

The biochemical mechanisms and enzymes involved in the processing of protein antigens for presentation by major histocompatibility complex class II molecules are poorly understood. This work describes the purification of a cathepsin D-like enzyme isolated from the murine B lymphoma cell line A20, a model antigen presenting cell. Two forms of cathepsin D-like enzyme were detected. One is soluble and located in the lysosome-enriched subcellular fraction. The other is membrane-associated and located in the endosome-enriched fraction. The membrane-associated form was purified to apparent homogeneity by affinity chromatography on pepstatin A-Sepharose. Its apparent molecular weight is 48,000, and its pH optimum is pH 4.0. Endosomal cathepsins are known to be involved in antigen processing in vivo, and the purified membrane-associated cathepsin D-like enzyme from A20 cells was used to study antigen processing in vitro. The enzyme cleaved a model protein antigen, Staphylococcus aureus nuclease (Nase) and thereby generated antigenic fragments recognized by a Nase-specific T cell hybridoma. Such studies have allowed us to begin to understand the role of protease specificity and T cell determinant selection.
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PMID:Isolation of a membrane-associated cathepsin D-like enzyme from the model antigen presenting cell, A20, and its ability to generate antigenic fragments from a protein antigen in a cell-free system. 810 81