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 nonconserved, hydrophilic N-terminal domain of eukaryotic DNA topoisomerase I (topo I) is dispensable for catalytic activity in vitro but essential in vivo. There are at least five putative nuclear localization signals and a nucleolin-binding signal within the first 215 residues of the topo I N-terminal domain. We have investigated physiological functions of the topo I N-terminal domain by fusing it to an enhanced green fluorescent protein (EGFP). The first 170 residues of the N-terminal domain allow efficient import of chimeric proteins into nuclei and nucleoli. The nucleolar localization of this protein does not depend on its interaction with nucleolin, whereas ongoing rDNA transcription clearly is crucial. Immunoprecipitation experiments reveal that the topo I N terminus (topoIN)-EGFP fusion protein associates with the TATA-binding protein in cells. Furthermore, DNA damage results in extensive nuclear redistribution of the topoIN-EGFP chimeric product. The redistribution is also p53-dependent and the N terminus of topo I appears to interact with p53 in vivo. These results show that the topo I localization to the nucleolus is related to the p53 and DNA damage, as well as changes in transcriptional status. Nucleolar release of topo I under conditions of cellular duress may represent an important, antecedent step in tumor cell killing by topoisomerase active agents.
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PMID:Subnuclear distribution of topoisomerase I is linked to ongoing transcription and p53 status. 1180 86

To investigate the importance of topoisomerases for transcription of the galactose induced genes, we have studied the expression of GAL1, GAL2, GAL7 and GAL10 in Saccharomyces cerevisiae cells deficient for topoisomerases I and II. We find that topoisomerases are required for transcriptional activation of the GAL genes, but are dispensable for ongoing transcription, eliminating a role of the enzymes in transcriptional elongation. Furthermore, we demonstrate that promoter chromatin remodeling of the GAL genes is unaffected in the topoisomerase deficient strain. However, the cells fail to successfully recruit RNA polymerase II due to an inability of the TATA-binding protein (TBP) to bind to the TATA box in these promoters. We therefore argue that topoisomerases are required for accurate assembly of the preinitiation complex at the promoters of the GAL genes.
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PMID:DNA Topoisomerases Are Required for Preinitiation Complex Assembly during GAL Gene Activation. 2617 27