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)

Polymorphic arylamine N-acetyltransferase in the liver determines the N-acetylation rate of arylamines, which has been implicated in the effects and toxicity of amine- and hydrazine-containing drugs. Recently we have demonstrated that there are four types of gene for polymorphic N-acetyltransferase and that gene 1 gives rise to high N-acetyltransferase activity, while gene 2, 3, and 4 correspond to low N-acetyltransferase activity. Analysis of four genes revealed that the point mutations in genes 2, 3, and 4 result in a loss of a restriction site: a BamHI site for gene 2, a TaqI site for gene 3, and a KpnI site for gene 4. Therefore all four genes can be discriminated by genomic Southern blot analysis and also by PCR amplification of the respective site followed by digestion with an appropriate endonuclease.
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PMID:[Molecular pharmacology of polymorphic arylamine N-acetyltransferase involved in the metabolism of arylamine drugs]. 161 74

Three genes encoding arylamine N-acetyltransferase were identified in Balb/c mice. All three genes were cloned from genomic DNA, sequenced and expressed in a bacterial expression system. Two of the genes corresponded to Nat-1 and Nat-2 which have been previously identified in A/J and C57B1/6 strains of mice (Martell et al., 1991). The new gene, designated Nat-3, can be distinguished from the other mouse Nat genes both by specific amplification using PCR and by restriction-endonuclease digestion. The products of all three genes are demonstrated to catalyse acetylation of aminofluorene and anisidine following expression in Escherichia coli.
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PMID:Arylamine N-acetyltransferase in Balb/c mice: identification of a novel mouse isoenzyme by cloning and expression in vitro. 754 52

The aarP gene has been identified in a search for activators of the 2-N-acetyltransferase [encoded by aac(2')-Ia] in Providencia stuartii. Introduction of aarP into P. stuartii on a multicopy plasmid resulted in a 9.9-fold increase in the accumulation of beta-galactosidase from an aac(2')-lacZ fusion. Northern (RNA) blot analysis demonstrated that this increased aac(2')-Ia expression occurred at the level of mRNA accumulation. The deduced AarP protein was 15,898 Da in size and exhibited significant homology to a number of transcriptional activators in the AraC/XyIS family, including TetD,Rob, MarA, and SoxS. The similarity of AarP to the MarA and SoxS proteins prompted an investigation to determine whether AarP is involved in activation of genes in either the multiple antibiotic resistance (Mar) phenotype or redox stress (SoxRS) system. Introduction of aarP on a multicopy plasmid into either P. stuartii or Escherichia coli conferred a Mar phenotype with higher levels of resistance to tetracycline, chloramphenicol, and ciprofloxacin. Multiple copies of aarP in E. coli also resulted in activation of the endonuclease IV gene (nfo), a gene in the SoxRS regulon of E. coli. The function of aarP in its single-copy state was addressed by using allelic replacement to construct an aarP::Cm disruption, which resulted in a fivefold reduction in the accumulation of aac(2')-Ia mRNA. Analysis of aarP regulation showed that aarP mRNA accumulation was slightly increased by exposure to tetracycline and dramatically increased in cells containing the aarB3 (aar3) mutation, which was previously shown to increase transcription of the aac(2')-Ia gene. (P.N. Rather, E. Oroz, K.J. Shaw, R. Hare, and G. Miller, J. Bacteriol. 175:6492-6498).
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PMID:Identification and analysis of aarP, a transcriptional activator of the 2'-N-acetyltransferase in Providencia stuartii. 776 49

The hepatic N-acetyltransferase enzyme encoded by the NAT2* gene locus is responsible for the human polymorphic acetylation of numerous arylamine or hydrazine-containing drugs and xenobiotics including AIDS-related therapeutic agents such as isoniazid and sulphonamides. The genetic basis underlying the human acetylation polymorphism has been extensively studied in several populations but native African populations were poorly documented. In the present study, 117 unrelated black Africans, namely Dogons from Mali and Gabonese, were investigated for NAT2* allelic variability and genotype distribution. Thirteen NAT2* alleles were unambiguously identified by combined use of allele-specific reamplifications and restriction endonuclease digestions. Our results confirm the African origin of G191->A substitution in the NAT2* coding region which was previously associated with slow acetylation in African-Americans. The finding of high allelic diversity in the studied populations is consistent with the hypothesis of a single African origin for NAT2*-associated polymorphism. Finally, no excess of the slow acetylator phenotype is predicted in these populations, implying no need for fitting NAT2* polymorphism-sensitive therapies to black Africans, compared to Caucasians.
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PMID:Genotyping of the polymorphic N-acetyltransferase (NAT2*) gene locus in two native African populations. 915 95

We report the complete sequence of two cosmids, SPBC19C7 (34815 bp insert, Accession No. AL023859) and SPBC15D4 (33203 bp insert, Accession No. AL031349), localized on chromosome II of the S. pombe genome. Twelve open reading frames (ORFs) were identified in SPBC19C7 and 16 in SPBC5D4. Two known genes were found on each cosmid: cyr1 and uve1 on SPBC19C7, encoding adenylate cyclase and a UV-endonuclease, respectively, and gpt and pho2 on SPBC15D4, encoding an N-acetylglucosamine-1-phosphate transferase and a4-nitrophenylphosphatase, respectively. Five ORFs similar to known proteins were found on SPBC19C7, and six on SPBC15D4. They include putative genes for a ubiquitin protein ligase, a prolyl-tRNA synthetase, a tRNA splicing endonuclease, a voltage-gated chloride channel, a mannosyl transferase, a kinesin-like protein, a histone transcriptional regulator, an N-acetyltransferase, a cystathionine gamma-synthase and a TFIID subunit. Two ORF products of SPBC15D4 do not have clear homologues: one encodes a putative transcriptional regulator with a binuclear zinc domain and the other a protein with six transmembrane domains. Two ORFs from SPBC15D4 are similar to unknown ORFs, one from Saccharomyces cerevisiae and the other from Caenorhabditis elegans. Finally, two ORFs of SPBC19C7 and six of SPBC15D4 correspond to orphan genes. The frequent occurrence of introns and the short and degenerated intron-exon boundaries consensus sequences significantly complicated ORF predictions. Two potential ORF-free regions spanning several kb were predicted, and a clustering of ORFs transcribed in the same orientation was observed.
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PMID:Sequence analysis of two cosmids from the right arm of the Schizosaccharomyces pombe chromosome II. 1066 67

The cytochrome P4501A subfamily (CYP1A) is involved in the metabolic activation of 7H-dibenzo[c,g]carbazole (DBC) and its tissue- and organ-specific derivatives, N-methyldibenzo[c,g]carbazole (MeDBC)and 5,9-dimethyldibenzo[c,g]carbazole (diMeDBC). In this study, we have evaluated the relationship between the tissue specificity and (32)P-postlabeled adduct patterns produced by these compounds by using a panel of Chinese hamster V79 cell lines stably expressing human CYP1A1 and CYP1A2 and/or N-acetyltransferase. Treatment of the parental cell lines V79MZ and V79NH, which are devoid of any CYP activity, with DBC and its derivatives did not result in detectable adducts. The highest DNA adduct levels were found in CYP1A1-expressing V79MZh1A1 cells after DBC and MeDBC treatment (24.5 +/- 7.2 and 16.2 +/- 3.6 adducts/10(8) nucleotides, respectively). Exposure of this cell line to DBC resulted in five distinct spots, while six spots with different chromatographic mobilities were detected in MeDBC-treated cells. DiMeDBC produced only very low levels of DNA adducts in V79MZh1A1 cells. DBC and MeDBC formed relatively low levels of DNA adducts in CYP1A2-expressing V79MZh1A2 cells (0.7 +/- 0.2 and 2.1 +/- 1.2 adducts/10(8) nucleotides, respectively). DBC formed three weak spots and MeDBC five spots in V79MZh1A2 cells, and all the spots had different chromatographic mobilities. In contrast, diMeDBC did not induce any DNA adducts in these cells, although diMeDBC induced a significant dose-dependent increase in micronucleus frequency under similar treatment conditions (r = 0.76; P < 0.001). The significant increase in DNA damage in the Comet assay following incubation of exposed cells with a repair-specific endonuclease (Fpg protein) suggests that base modifications such as 8-oxodG or Fapy-adducts might be responsible for the genotoxicity of diMeDBC in V79MZh1A2 cells. The similarities between the DNA adduct patterns produced by DBC and MeDBC in V79MZh1A1 and V79MZh1A2 cells suggest that biotransformation mediated via CYP1A1 and CYP1A2 might depend on a PAH-type pathway involving the aromatic ring system.
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PMID:DNA adduct formation by 7H-dibenzo[c,g]carbazole and its tissue- and organ-specific derivatives in Chinese hamster V79 cell lines stably expressing cytochrome P450 enzymes. 1553 62