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)

We have located presumptive chromosomal loop anchorage elements within the mouse heavy chain immunoglobulin locus. Analysis of 31 kilobases spanning diversity, joining, enhancer, switch, and the mu and delta constant regions reveals that only a single 1-kilobase segment exhibits specific binding to nuclear matrices. It is of particular significance that the transcriptional enhancer element resides within this matrix association region (MAR). Fine structure mapping indicates that binding is mediated by A+T-rich approximately 350-base pair segments that reside on either side of the enhancer. The MAR sequences residing 5' of the enhancer contain topoisomerase II consensus sequences like the MAR located upstream of the kappa light chain gene enhancer. The heavy chain gene MARs, however, exhibit a lower affinity for matrix association compared to the kappa gene MAR. Significantly, the juxtaposition of enhancer elements with MARs appears to be evolutionarily conserved within the immunoglobulin genes, suggesting that MARs may act as positive and/or negative regulators of enhancer function.
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PMID:The enhancer of the immunoglobulin heavy chain locus is flanked by presumptive chromosomal loop anchorage elements. 303 Oct 52

We previously identified a B cell-specific protein-DNA complex 5' of an immunoglobulin mu heavy chain promoter. The sequences to which this protein complex bound were required for induction of immunoglobulin mRNA levels with interleukin-5 + antigen. Further studies identified a second sequence 5' of these regulatory sequences that bound to both the nuclear matrix and to a similar interleukin-5 + antigen inducible protein complex. Therefore, we sought to identify the putative regulatory proteins that comprised this DNA-binding complex. In this study, we have used anti-topoisomerase II antibodies to demonstrate that one of the proteins found in the interleukin-5 + antigen inducible complexes is serologically related to topoisomerase II. To our knowledge, this is the first report where a topoisomerase II related protein participates in an inducible mobility shifted protein-DNA complex. These data suggest a model in which the enhanced immunoglobulin gene transcription observed after treatment with interleukin-5 + antigen might be explained by the induction of a protein complex that acts to relieve torsional stress along the gene.
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PMID:A topoisomerase II-like protein is part of an inducible DNA-binding protein complex that binds 5' of an immunoglobulin promoter. 841 93

Autoantibodies to centromere proteins (anti-CENPs) and to topoisomerase-I are highly specific for scleroderma. Unlike most autoantibodies in other diseases, these autoantibodies are mutually exclusive. We have analysed the idiotypes (Ids) expressed by anti-CENP-B, antitopoisomerase-I, and IgGs from 20 scleroderma patients. Rabbit anti-Ids were prepared to antitopoisomerase-I from two scleroderma patients, and to anti-CENP-B from four patients. These six anti-Ids were used to study the purified autoantibodies from 20 scleroderma patients: four antitopoisomerase-I, 10 anti-CENP-B, and six purified IgG from scleroderma patients who were negative for both autoantibodies. In addition, we studied sera from 40 normal autoantibody-negative controls, and sera and purified immunoglobulins from 17 systemic lupus erythematosus (SLE) patients containing high titres of anti-double-stranded DNA, and/or autoantibodies to extractable nuclear antigens (ENA). Using direct binding, and competitive inhibition ELISAs and immunoblots, we identified an Id present in the heavy chains of all the affinity-purified antitopoisomerase-I, and anti-CENP-B. Interestingly, this Id was also present in the immunoglobulins of the scleroderma patients who had neither of the two autoantibodies. By contrast, cross-reactive Id-EM was not found in the sera or immunoglobulins from 17 SLE patients, or in the sera from 40 normal subjects. Several samples from two patients showed that this cross-reactive Id-EM was stable over time. The scleroderma disease-specific autoantibodies may be identified through a common structural feature at the variable region of the heavy chain: cross-reactive Id-EM.
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PMID:A cross-reactive idiotype in scleroderma. 918 86

A study was made of geno- and phenotypic changes, associated with of multidrug resistance development in murine 1F7 hybridoma cells, selected for adriamycin and ethidium bromide resistance (1F7-EBR and 1F7-ADR). In both cell lines overexpression of mdr1 gene was observed, while amplification of mdr1 gene was detected only in 1F7-ADR cells. Karyotypic analysis revealed in resistant cells the presence of a specific marker M45 absent from parental cells, thus suggesting its selective importance. The M45 length instability, as well as the presence of a distal typical homogeneously stained region in it provide an evidence for a link between M45 and mdr1 gene amplification. The frequency of double minute chromosomes in parental lines was the same as in multidrug resistant lines. In 1F7-ADR cells, in contrast with 1F7-EBR cells, the enhancement of immunoglobulin production and the increase in immunoglobulin gamma 2b heavy chain gene expression were observed, which correlated with a decline in DNA-topoisomerase II activity.
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PMID:[The genome structure and phenotypic characteristics of murine hybridoma 1F7 cells selected in the presence of adriamycin and ethidium bromide]. 949 May 14

The first step of Ig heavy chain class switch recombination (CSR) is considered to be DNA double strand break (DSB) formation in the two switch (S) regions (S(mu) and downstream S(H)), although the underlying mechanism is unknown. Recently, it has been demonstrated that at least Spo11, a homolog of the novel type II topoisomerase (topo VI) that catalyzes DSB formation, is involved in the initiation of meiotic recombination of Saccaromyces cerevisiae. In the present study, we examined whether the mouse homolog of Spo11 is induced in normal mouse mu(+)B-cells by stimuli that cause an early step of CSR, germline C(H) transcription, and subsequent CSR. Two CSR systems were used: IgA CSR induced by all-trans retinoic acid, IL-5, and LPS, and IgG1 CSR induced by IL-4 and LPS. Germline transcript and mouse Spo11 expression were analyzed by RT-PCR. In both systems, first germline transcripts were clearly detected on day 2 and then Spo11 was detected on day 3, increasing thereafter with time. The time course of changes in Spo11 expression coincided with that of CSR. Spo11 seems to be induced by CSR-inducing stimuli, regardless of the direction of CSR. These results suggested that mouse Spo11 might participate in the initiation step of CSR.
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PMID:Mouse homolog of Saccharomyces cerevisiae spo11 is induced in normal mu(+)B-cells by stimuli that cause germline C(H) transcription and subsequent class switch recombination. 1087