Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An enconuclease activity that reacts with x-irradiated DNA is present in extracts of E. coli. By using centrifugal methods to monitor the conversion of the supercoiled, circular double-stranded DNA for phage phi-x-174 (replicative form) or PM2 to the relaxed circular form it was possible to quantitate the rate of radiation induced endonuclease-sensitive sites in the DNA. For every single-strand break induced by x-rays under aerobic irradiation conditions, there is approximately one induced site sensitive to this endonuclease activity. Under irradiation conditions (addition OF Potassium iodide) that dramatically reduce rates of single-strand breaks and "alkalilabile" lesions, the number of endonuclease-sensitive sites relative to single-strand breaks increase approximatley 4-fold. This nuclease is present in several strains of E. coli B and K12, including mutants deficient in DNA polymerase I, recombination gene products (rec mutants), ultraviolet light incision enzyme (uvr A mutant), and endonuclease II. It is suggested that this endonuclease may be involved in an excision repair process for damages incurred in DNA by ionizing radiation.
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PMID:Endonucleolytic incision of x-irradiated deoxyribonucleic acid by extracts of Escherichia coli. 109 50

Plasmid isolation was used to refine the epidemiologic analysis for 168 shigellosis cases in Pima County, Ariz. Plasmids of less than 20 kb were used for comparison of plasmid profiles. Plasmid patterns for each species were distinct. A total of 57 of 74 (77%) Shigella flexneri strains could be placed into seven plasmid patterns, 70 of 79 (89%) Shigella sonnei strains could be placed into seven patterns, 12 Shigella boydii strains could be placed into six patterns, and each of 3 Shigella dysenteriae strains differed. There was a correlation between plasmid patterns and serotypes for S. flexneri, and multiple plasmid patterns were found in serotypes 1, 2, and 6, offering a refinement beyond serotyping. In previous studies we found an association between Mexican travel and an S. sonnei 5.1-kb plasmid. When this plasmid was used as a probe, strong homology was seen with numerous small plasmids in all Shigella species: restriction endonuclease analysis revealed a 1.1-kb AvaI-AvaII fragment common to various plasmids of S. sonnei. S. flexneri, and S. boydii independent of species. Of 34 Pima County Shigella isolates from the mid-1970s. 8 showed plasmid patterns similar to those of the recent isolates. Some plasmids from S. sonnei, S. flexneri, and S. boydii strains isolated in the 1970s also contained the AvaI-AvaII fragment. The conservation of this specific fragment in our population for more than 12 years suggests that it may contain genes important in virulence or survival.
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PMID:Molecular epidemiology of Shigella infections: plasmid profiles, serotype correlation, and restriction endonuclease analysis. 184 48

The mitochondrial DNA (mtDNA) sequence variation of the South American Ticuna, the Central American Maya, and the North American Pima was analyzed by restriction-endonuclease digestion and oligonucleotide hybridization. The analysis revealed that Amerindian populations have high frequencies of mtDNAs containing the rare Asian RFLP HincII morph 6, a rare HaeIII site gain, and a unique AluI site gain. In addition, the Asian-specific deletion between the cytochrome c oxidase subunit II (COII) and tRNA(Lys) genes was also prevalent in both the Pima and the Maya. These data suggest that Amerindian mtDNAs derived from at least four primary maternal lineages, that new tribal-specific variants accumulated as these mtDNAs became distributed throughout the Americas, and that some genetic variation may have been lost when the progenitors of the Ticuna separated from the North and Central American populations.
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PMID:Amerindian mitochondrial DNAs have rare Asian mutations at high frequencies, suggesting they derived from four primary maternal lineages. 196 8

Recently, a missense mutation replacing tryptophan with arginine at codon 64 of the beta 3-adrenergic receptor gene was shown to be associated with insulin resistance in nondiabetic subjects and to an earlier onset of NIDDM in Pima Indians. We studied whether the codon 64 amino acid polymorphism of the beta 3-adrenergic receptor gene in a cohort of young healthy Danes was associated with high birth weight, accelerated weight gain during childhood and adolescence, present obesity, or impaired insulin sensitivity. The protocol included 380 unrelated white subjects in whom insulin sensitivity and secretion were measured during a combined intravenous glucose and tolbutamide tolerance test. A number of biochemical and anthropometric characteristics were determined for each subject. The subjects were genotyped for the codon 64 polymorphism by applying polymerase chain reaction restriction fragment-length polymorphism screening with the use of endonuclease BstN1. The allelic frequency of the mutated allele was 7% (95% CI: 5-10%), and it was similar in obese and nonobese subjects. The beta 3-adrenergic receptor gene variant was not related to birth weight or weight gain during childhood or adolescence. In its heterozygous form, the gene variant was not associated with an altered insulin sensitivity index (SI) or other features of the insulin resistance syndrome (BMI, blood pressure, fasting serum lipid levels, or fasting serum fibrinolytic variables). Three homozygous carriers of the polymorphism were identified, and each had a significantly higher BMI (27.4 +/- 1.3 vs. 23.5 +/- 3.7 kg/m2 [mean +/- SD]; P = 0.032), lower SI [4.9 +/- 2.9 vs. 15.4 +/- 9.0 10(-5) x (min x pmol/l)-1; P = 0.013], and higher fasting serum C-peptide (730 +/- 155 vs. 471 +/- 158 pmol/l; P = 0.016) than the wild-type carriers. The homozygous carriers also had significantly higher levels of fasting serum triglyceride (P = 0.042) and serum LDL cholesterol (P = 0.013). When adjustments were made for age, sex, BMI, and VO2max in a multiple regression analysis, a significantly negative association was found between homozygosity for the codon 64 variant and the SI (P = 0.009). We conclude that in young healthy Danes, the homozygous form but not the heterozygous form of the codon 64 amino acid polymorphism of the beta 3-adrenergic receptor may be associated with obesity and, independent of BMI, with a low SI. Since only three homozygous carriers were identified among 380 subjects, the results must be interpreted with caution, and studies of larger population samples are needed.
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PMID:Insulin sensitivity and body weight changes in young white carriers of the codon 64 amino acid polymorphism of the beta 3-adrenergic receptor gene. 869 Jan 60

Circular concatemerization of the recombinant adeno-associated virus (rAAV) genome has been suggested as the predominant process facilitating long-term rAAV transduction in muscle. A recent study (S. Song, P. J. Laipis, K. I. Berns, and T. R. Flotte, Proc. Natl. Acad. Sci. USA 98:4084-4088, 2001) with SCID mice, which are defective in the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), has suggested that DNA-PKcs regulates the removal of free rAAV vector ends in muscle tissue. In the present study, we have sought to evaluate whether a lack of DNA-PKcs activity reduces circularization of rAAV genomes in SCID muscle and whether such a reduction alters the directivity of heterodimerization. Consistent with the previous report, linear rAAV genomes and free vector ends were detected only in DNA-PKcs-deficient muscle by Southern blotting. Appreciable amounts of circular rAAV genomes were detected in both DNA-PKcs-deficient and wild-type muscle samples by Southern blotting and bacterial trapping experiments. The existence of double-D inverted terminal repeat circular intermediates in SCID and wild-type muscles was also supported by their sensitivity to T7 endonuclease I digestion. However, DNA-PKcs-deficient muscle did demonstrate a approximately 50% reduction in the abundance of rescued circular genomes, despite equivalent levels of single rAAV transduction seen in wild-type animals. Dual trans-splicing lacZ vectors were used to functionally evaluate directional head-to-tail intermolecular viral genome concatamerization in vivo. Although AAV genomes are processed differently in SCID and wild-type muscles, a comparable level of trans-splicing-mediated beta-galactosidase expression was observed in both strains, suggesting that both circular and linear AAV concatemers may have contributed to the trans-splicing-mediated transgene expression. In summary, we have shown that SCID skeletal muscle retains a fairly high capacity to form circular genomes, despite a significant increase in linear vector genomes. Furthermore, the alteration in equilibrium between circular and linear concatemer genomes caused by the lack of DNA-PKcs activity does not appear to significantly affect the efficiency of dual-vector gene expression from head-to-tail linear and/or circular heterodimers.
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PMID:Consequences of DNA-dependent protein kinase catalytic subunit deficiency on recombinant adeno-associated virus genome circularization and heterodimerization in muscle tissue. 1266 82