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)

The mechanisms involved in the restriction of the cellular tropism of HIV-1 to cells of primate origin remain to be clearly defined. However, a number of studies have shown that this is determined not only at the level of the cellular receptor(s) or virus entry, but at a number of additional and later stages in virus replication. We have recently reported that the reverse transcription of HIV-1 RNA is markedly enhanced by the association of the gag encoded nucleocapsid p15 protein and cellular topoisomerase 1. In the present study we have now investigated if the recruitment of cellular topoisomerase I during virus replication is important in determining the cellular tropism of HIV-1. Employing a stable murine cell line, L929, expressing both human CD4 and topoisomerase I, it could be demonstrated that effective proviral DNA synthesis occurred following infection. In contrast in cells expressing only human CD4 proviral DNA synthesis was not detected. In addition we have co-expressed fusin, a protein known to act as an accessory factor as the virus entry stage in infection of T cell tropic HIV-1, to support viral entry completely. However no progeny virus could be detected after HIV-1 infection. These results suggest that reverse transcription in vivo is critically dependent on the presence of cellular topoisomerase I, and support the view that involvement of this enzyme is in HIV-1 replication. Moreover the findings suggest that other factors which remained to be identified, are involved in restricting HIV-1 replication in non-primate cells.
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PMID:The role of topoisomerase I in HIV-1 replication. 920 86

The burdock element is known to be the 2.6-kb insertion into the same region of the cut locus in 12 independently obtained ct-lethal mutants. Here we have determined the complete sequences of this insertion and of the hot spot region. It was found that the burdock is a short retrotransposon with long terminal repeats and a single open reading frame (ORF). The polypeptide encoded by the burdock ORF contains two adjacent regions homologous to the gag and pol polyproteins of the gypsy mobile element. The burdock insertion interrupts the short ORF of the cut locus. The target site sequence of the burdock insertions is similar to the Drosophila topoisomerase II cleavage site.
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PMID:Burdock, a novel retrotransposon in Drosophila melanogaster, integrates into the coding region of the cut locus. 928 7

Scaffold or matrix attachment regions (S/MARs) are noncoding genomic DNA sequences displaying in vitro selective binding affinity for nuclear scaffold. They have been reported to be involved in the physical attachment of genomic DNA to the nuclear scaffold, and thus in the organization of the chromatin in functional loops or domains, and in the regulation of gene expression. In this work, we report the identification of an S/MAR in a woodchuck chromosomal locus, named b3n, previously described as a recurrent site of woodchuck hepatitis virus (WHV) DNA integration in woodchuck hepatocellular carcinoma (HCC). The 4.3-kb sequence of this locus contains several Alu-like repeats and a gag-like coding region with frameshift mutations. Computer analysis revealed the presence of a region with unusually high AT content, typical of most S/MARs, and of specific motifs (A boxes, T boxes, topoisomerase II sites, and unwinding elements) overlapping or in proximity to the region with high AT content, predicting that b3n might contain an S/MAR. Fragments of the b3n locus were isolated by conventional and inverse PCR techniques. In in vitro binding experiments with both heterologous and autologous scaffold preparations, a 592-bp fragment spanning the region rich in S/MAR features showed marked scaffold affinity, which was specific when autologous scaffolds were used. The presence of an S/MAR at the b3n locus and its nature as a recurrent WHV integration site in HCC suggest the involvement of S/MAR elements in some of the mechanisms leading to liver oncogenesis.
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PMID:Identification of scaffold/matrix attachment region in recurrent site of woodchuck hepatitis virus integration. 965 45