Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several 5-substituted 2-pyrimidinone 2'-deoxyribonucleoside (PdR) analogs were examined for their anti-herpes simplex virus (HSV) activity in cell culture. The order of potency of their antiviral activities against HSV type 1 (HSV-1) and HSV-2 was iodo PdR approximately ethynyl PdR approximately propynyl PdR. The antiviral action of iodo PdR is dependent on the ability of HSV to induce virus-specified thymidine kinase in infected cells. Several HSV-1 variants with altered thymidine kinase changed their sensitivity to iodo PdR, whereas HSV-1 variants with altered DNA polymerase were as sensitive as the parental virus to iodo PdR. Continuous presence of iodo PdR for more than one virus replication cycle was required for optimal antiviral activity. Iodo PdR (100 microM) had no activity against Epstein-Barr virus DNA replication in P3HR-1 cells. With an oral, an intraperitoneal, or a subcutaneous route of injection, iodo PdR administered twice a day for 2.5 days could prevent the death of mice infected with HSV-2. This in vivo activity is unlikely to be related to the potential conversion of iodo PdR to iododeoxyuridine, since iodo PdR is not a substrate of xanthine oxidase.
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PMID:Anti-herpes simplex virus activity of 5-substituted 2-pyrimidinone nucleosides. 254 79

Mechanism-based enzyme inactivator, alanine racemase, S-adenosylhomocysteine hydrolase, D-amino acid aminotransferase, gamma-aminobutyric acid aminotransferase, arginine decarboxylase, aromatase, L-aromatic amino acid decarboxylase, dihydrofolate reductase, dihydroorotate dehydrogenase DNA polymerase I, dopamine beta-hydroxylase, histidine decarboxylase, beta-lactamase, monoamine oxidase, ornithine decarboxylase, serine proteases, testosterone 5 alpha-reductase, thymidylate synthetase, xanthine oxidase.
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PMID:The potential use of mechanism-based enzyme inactivators in medicine. 306 67

DNA polymerase beta is required in mammalian cells for the predominant pathway of base excision repair involving single nucleotide gap filling DNA synthesis. Here we examine the relationship between oxidative stress, cellular levels of DNA polymerase beta and base excision repair capacity in vitro , using mouse monocytes and either wild-type mouse fibroblasts or those deleted of the DNA polymerase beta gene. Treatment with an oxidative stress-inducing agent such as hydrogen peroxide, 3-morpholinosydnonimine, xanthine/xanthine oxidase or lipopolysaccharide was found to increase the level of DNA polymerase beta in both monocytes and fibroblasts. Base excision repair capacity in vitro , as measured in crude cell extracts, was also increased by lipopolysaccharide treatment in both cell types. In monocytes lipopolysaccharide-mediated up-regulation of the base excision repair system correlated with increased resistance to the monofunctional DNA alkylating agent methyl methanesulfonate. By making use of a quantitative PCR assay to detect lesions in genomic DNA we show that lipopolysaccharide treatment of fibroblast cells reduces the incidence of spontaneous DNA lesions. This effect may be due to the enhanced DNA polymerase beta-dependent base excision repair capacity of the cells, because a similar decrease in DNA lesions was not observed in cells deficient in base excision repair by virtue of DNA polymerase beta gene deletion. Similarly, fibroblasts treated with lipopolysaccharide were more resistant to methyl methanesulfonate than untreated cells. This effect was not observed in cells deleted of the DNA polymerase beta gene. These results suggest that the DNA polymerase beta-dependent base excision repair pathway can be up-regulated by oxidative stress-inducing agents in mouse cell lines.
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PMID:Up-regulation of base excision repair correlates with enhanced protection against a DNA damaging agent in mouse cell lines. 951 96