Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Werner's syndrome (WS) is an inherited disease with clinical symptoms which resemble premature aging. The Werner's syndrome gene (WRN), which is located on human chromosome 8p12, encodes a predicted protein of 1432 amino acids and shows significant similarity to DNA helicases. We have cloned the full-length mouse cDNA homologue of the human WRN gene encoding a predicted protein of 1320 amino acids and have obtained a full-length 70 kb genomic clone containing the moWRN gene. This gene has been mapped to chromosome 8A3 in mice. The expression of the moWRN gene was increased during apoptosis after IL-2 deprivation, and decreased in the spleen of aged mice. Lymphoid cells isolated from a patient with WS exhibited increased apoptosis after incubation with anti-Fas but not after incubation with the topoisomerase inhibitor VP16. RNase protection reviled dysregulation of the ICE family of apoptosis molecules in the WS cell line. These results indicate that the WS helicase is involved in certain pathways of apoptosis, and defective WS gene expression leads to accumulation of cells that are highly susceptibility to Fas-induced apoptosis.
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PMID:Effect of age and apoptosis on the mouse homologue of the huWRN gene. 968 77

We have successfully expressed enzymatically active plant topoisomerase II in Escherichia coli for the first time, which has enabled its biochemical characterization. Using a PCR-based strategy, we obtained a full-length cDNA and the corresponding genomic clone of tobacco topoisomerase II. The genomic clone has 18 exons interrupted by 17 introns. Most of the 5' and 3' splice junctions follow the typical canonical consensus dinucleotide sequence GU-AG present in other plant introns. The position of introns and phasing with respect to primary amino acid sequence in tobacco TopII and Arabidopsis TopII are highly conserved, suggesting that the two genes are evolved from the common ancestral type II topoisomerase gene. The cDNA encodes a polypeptide of 1482 amino acids. The primary amino acid sequence shows a striking sequence similarity, preserving all the structural domains that are conserved among eukaryotic type II topoisomerases in an identical spatial order. We have expressed the full-length polypeptide in E. coli and purified the recombinant protein to homogeneity. The full-length polypeptide relaxed supercoiled DNA and decatenated the catenated DNA in a Mg(2+)- and ATP-dependent manner, and this activity was inhibited by 4'-(9-acridinylamino)-3'-methoxymethanesulfonanilide (m-AMSA). The immunofluorescence and confocal microscopic studies, with antibodies developed against the N-terminal region of tobacco recombinant topoisomerase II, established the nuclear localization of topoisomerase II in tobacco BY2 cells. The regulated expression of tobacco topoisomerase II gene under the GAL1 promoter functionally complemented a temperature-sensitive TopII(ts) yeast mutant.
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PMID:Molecular characterization of a nuclear topoisomerase II from Nicotiana tabacum that functionally complements a temperature-sensitive topoisomerase II yeast mutant. 1455 65