Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT01586 (G418)
 2,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

True gamma or gamma 2 genes, unlike alpha, beta, and gamma 1 (beta gamma) genes of herpes simplex virus 1 (HSV-1), stringently require viral DNA synthesis for their expression. We report that gamma 2 genes resident in cells were induced in trans by infection with HSV-1 but that the induction did not require amplification of either the resident gene or the infecting viral genome. Specifically, to test the hypothesis that expression of these genes is amplification dependent, we constructed two sets of gamma 2-thymidine kinase (TK) chimeric genes. The first (pRB3038) consisted of the promoter-regulatory region and a portion of 5'-transcribed noncoding region of the domain of a gamma 2 gene identified by Hall et al. (J. Virol. 43:594-607) in the HSV-1(F) BamHI fragment D' to the 5'-transcribed noncoding and coding regions of the TK gene. The second (pRB3048) contained, in addition, an origin of HSV-1 DNA replication. Cells transfected with either the first or second construct and selected for the TK+ phenotype were then tested for TK induction after superinfection with HSV-1(F) delta 305, containing a deletion in the coding sequences of the TK gene, and viruses containing, in addition, a ts lesion in the alpha 4 regulatory protein (ts502 delta 305) or in the beta 8 major DNA-binding protein (tsHA1 delta 305). The results were as follows: induction by infection with TK- virus of chimeric TK genes with or without an origin of DNA replication was dependent on functional alpha 4 protein but not on viral DNA synthesis; the resident chimeric gene in cells selected for G418 (neomycin) resistance was regulated in the same fashion; the chimeric gene recombined into the viral DNA was regulated as a gamma 2 gene in that its expression in infected cells was dependent on viral DNA synthesis; the gamma 2-chimeric genes resident in the host and in viral genomes were transcribed from the donor BamHI fragment D' containing the promoter-regulatory domain of the gamma 2 gene. The significance of the differential regulation of gamma 2 genes in the environments of host and viral genomes by viral trans-acting factors is discussed.
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PMID:gamma 2-Thymidine kinase chimeras are identically transcribed but regulated a gamma 2 genes in herpes simplex virus genomes and as beta genes in cell genomes. 298 55

Poly(ADP-ribose)polymerase (PARP) is a DNA-binding protein that is activated upon induction of DNA breaks and supposed to play a role in DNA repair. To elucidate the effect of overexpression of PARP on the resistance of cells to mutagens, Chinese hamster ovary cells (both the line CHO-9 and the mutagen-hypersensitive derivative 27-1) were transfected with the human PARP cDNA along with pSV2neo. Treatment of the transfected cell population with a high dose of MNNG and selection with G418 gave rise to a significant increase of neo+ clones, as compared to the control transfection with pSV2neo + salmon sperm DNA. The frequency of survivors in these mass culture experiments was lower, however, than after transfection with the bacterial ada gene encoding the DNA repair protein O6-alkylguanine-DNA alkyltransferase. Thus transfection of PARP cDNA in CHO cells is only weakly effective in inducing alkylation resistance. This was confirmed by analyzing the mutagen resistance of individual PARP transfectant clones derived from CHO-9 and 27-1 cells that expressed increased levels of PARP mRNA, protein and PARP activity. These strains were slightly more resistant to the toxic effect of MMS and showed a reduced frequency of MMS-induced chromosomal aberrations. CHO-9-PARP transfectants also gained resistance to UV. From these data we conclude that, in CHO cells, PARP is limiting in handling critical lesions during the repair process and that increase of the amount of PARP protein can elicit some protection against genotoxic effects of mutagens.
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PMID:Effect of transfection of human poly(ADP-ribose)polymerase in Chinese hamster cells on mutagen resistance. 751 39